It wasn't until 1508,  four years after, that any interest to colonize Tierra Firme was attempted by the King of Spain and the Council of the Indies. Herrera, the official historian of the Spanish Court, reported that the king was very interested in having Tierra Firme colonized; but, at the time, he was preoccupied with the wars in Spain. To finance the wars, a source of gold had to be found, and Castilla del Oro, would be the perfect place to find it. 

At that time, there were two Spaniards interested in colonizing Tierra Firme. One was Alonso de Ojeda and the other was Diego de Nicuesa. Ojeda, lacked the funds to attempt such an enterprise, and joined forces with Juan de la Cosa, who had been with Columbus and others, on voyages to the New World, and had accumulated a small fortune from these exploits.

Nicuesa had the advantage of being richer than Ojeda and a member of the Spanish Court. He held the office of The Royal Carver, was one of the most pretentious individuals in Madrid, was very popular with the ladies at Court, and was a gentleman of unquestioned integrity and valor. But he lacked  training for the hard work that was to come. Nicuesa was very arrogant and self assuming, and would soon prove to lack the ability to lead men during a crises. He proved to be a stubborn fool, who mistrusted his men, and succeeded in turning his friends against him. He set aside the Royal Carving Knife for the sword of the Conqueror.

At this time Merit and Favoritism balanced each other in the eyes of the king. Not being able to select between them,  he appointed them both. Nicuesa was given the province of Castilla del Oro, from Cape Gracias a Diós to the border of Nueva Andalusia. Ojeda was given Nueva Andalusia from Cape de la Vela to the domains of Nicuesa. The dividing line between these two provinces was left for them to fight out.

In the fall of 1509, the two governors met in Española and started quarreling right away. The king complicated matters further, by giving them jointly, the Island of Jamaica as a  source of provisions. This only served to upset the governor of Española, Diego Colon, the son of the Great Admiral. Diego claimed all lands discovered by his father, which included Jamaica. This made him so hostile to the two new governors, that instead of helping them with ships and men, as the king had ordered, he did all he could to hinder them and did everything he could to arouse the jealousy between them. With Juan de la Cosa as a mediator, they agreed to accept the Darien River, (now called the Atrato River) as the boundary between their provinces.

Nicuesa, having the most ready cash available, was able to outbid Ojeda for ships and equipment. On the other hand, Ojeda's experience in the area, his reputation and personal charisma  attracted the best and most able of the volunteers. Ojeda was able to enlist the Bachelor of Law, Martin Fernandez de Enciso to his enterprise. This attorney had amassed a fortune in the few years of colonial practice. For his financial support, Ojeda made him, "Alcalde Major", Chief Justice of the vice-royalty of Nueva Andalusia.

On November 12, 1509, Ojeda set sailed from Española, with two ships, two brigantines, three hundred men and twelve brood mares. A few days later, Nicuesa set sail with two large ships, two brigantines, a caravel, seven hundred men and six horses. Nicuesa led a better equipped and lager expedition. Unfortunately, his force was made up mostly of men fresh from Spain, lacking experience, and not  hardened for the hard work before them.  

Left behind in Española, was Rodrigo Enríquez de Colmenares, one of Nicuesa's lieutenants. He was to follow Nicuesa to Castilla del Oro, as soon as he could recruit more men and supplies for the expedition.  

When Ojeda's expedition reached the province of Nueva Granada, near the present city of Cartagena, Colombia, he proceeded to claim it in the name of Spain and himself. He tried to convert the natives to Catholicism and to renounce their chief and accept the King of Spain, as their sovereign. When they would not, he massacred those he could, while the rest took refuge in the jungles. Later, he attacked their village, and the natives scattered again. This time, they counter attacked the Spaniards from their hiding places in the jungle, with poison arrows, and routed them. Most of Ojeda's force was killed, including Juan de la Cosa. The sailors left on the ships were worried about the long absence of the landing party when Ojeda was spotted on the beach. He was in a sorry state, hungry, wounded and without his men. 

At this point, they spotted some sails in the horizon, it was the Nicuesa's fleet, that was lost, and trying to find Castilla del Oro. Ojeda feared that Nicuesa would take advantage of his distress. But Nicuesa. in the only noble incident related to him, sent word that "A Spanish hidalgo does not harbor malice against a prostrate foe." He sent a party of men to help Ojeda avenge the death of Juan de la Cosa, and his men. They surprised the Indians, who were feasting in their village, in celebration of their victory, and massacred every last man, women and child. The Spaniards were upset by the sight of the corpse of de la Cosa, horribly bloated and discolored as a result of the poisoned arrows. Nicuesa's men share of the booty was over thirty-five thousand dollars. Nicuesa left some provisions for Ojeda, and continued on his way

When he picked up the coast of the Isthmus, he ordered his two large ships to maintain themselves well out to sea, as a precaution. Lope de Olano, his second in command, was ordered to keep in sight of him in the brigantine, while he in the little caravel would scout the coast close to shore. With Nicuesa in command, they sailed pass the Veraguas River by mistake. Some of the sailors who had been with Columbus, seven years before, realized the error. They informed Nicuesa that they had gone past the Veraguas River and urged him to turn back. But with the since he believed that he was infallible and knew everything, he would not heed their advice and ordered his men to pushed on.  

Sailing further and further away from their objective, a sudden storm, for which this coast of Panama is famous for, forced the ships to tack further out to sea, away from the shore. Nicuesa, in his little caravel, had to seek shelter in a little cove at the mouth of a  river. That night, a sudden wave wrecked the caravel on some reefs. The men with Nicuesa were able to make it safely to shore, in the long boat, after several trips between the beach and the sinking caravel. In the mishap they lost all of their provisions, including most of their clothes.

The next morning, Olano and his brigantine, was nowhere in sight, since they had been pushed further out to sea. The little group of stranded men waited on the beach for several days to be rescued. But Olano never come for them. This was the same man had been one of the mutineers against Columbus, in the Rebellion of Santo Domingo, and was an untrustworthy person. He was accused of deliberately deserting Nicuesa, in the hope of inheriting his governorship. Whatever his motives were, he rejoined the ships after the storm, and informed them  that the caravel had been lost with all hands, during the storm.

Nicuesa and the crew of the caravel found themselves in an exceedingly precarious position. They had no food, other than what they could find in the jungle and the sea. The only means of transportation was the long boat on which they escaped the sinking caravel. Believing that their only salvation was meeting the other ships at the Veraguas River, which had been agreed upon as a rendezvous in case of separation, Nicuesa insisted on proceeding, again, he insisted that they continue westward. The sailors, who knew they had passed the Veraguas River, urged him to turn back. But believing that he was right, marched his company westward along the beach. There were four men in the long boat, rowing along close to the shore, within sight of those proceeding by land. The long boat was used to ferry them across the many rivers that empty into the sea.

The group made very little progress, with the constant rains, very little to eat except what they were able to get from the sea, and occasional cocoanuts and fruits they could find. The hardships encountered was too much for the noble cavaliers, who were not prepared or built for hard work.

One day as they were passing under a high cliff a spear was thrown from the overhanging trees. It pierced the heart of Nicuesa's little page. The boy's white satin jacket, torn by the thorns, covered in mud of the rivers, had proved to be a good target for the Indian. This was the only time they had any contact with the inhabitants of the area, and they never saw who they were attacked by.

One evening they came to a large river, just before sundown and there was not enough daylight left to ferry them across, so they camped at the mouth of the river. The next morning the long boat had disappeared. Their situation was worse due to the fact that they were not on the mainland, but on a small islet at the delta of the river. Marooned on this island, without provisions, entirely dependent on shell-fish for food and pools of trapped rain water for drinking, most of them gave up hope. Nicuesa did what could be done to keep up their spirits. On three different times he persuaded them to build a raft, but they had no tools, or nails. Each time they put their raft in the surf, it was smashed to pieces. The stayed there for a long time, estimated to be above three months. Many of he men died from exposure and drinking the brackish water, to quench their thirst. Those that were alive, lacked the strength to walk, and resorted to crawling on all four

Fortunately, the long boat that disappeared had not foundered at sea and Ribero, the boatswain, and his three companions not guilty of malicious desertion. They knew the coast, knew that Nicuesa was leading his men further and further from help and salvation. So, taking things into their own hands, they slipped away during the night to see if they could reach the Veraguas River and bring back a rescue party.

When Olano assumed command of the main force of the expedition, he led them to the Belen River. They started a new settlement on the same spot where Columbus and his brother Bartholomew had tried to found one seven years before. They even found the remains of the Gallega, the ship left behind by Columbus. After incredible hardships, Ribero and his comrades found the encampment. Olano may not have happy to hear the news that his governor, Nicuesa was still alive, but he at once sent the brigantine to rescue them.

It arrived just in time, since Nicuesa and the remnant of his company were too weak to signal from shore. They had watched in vain for a long time for a sail that would rescue them, and could hardly believe it, when they were carried on board and fed.

Nicuesa's first act on rejoining his colony was to order the imprisonment of Olano. Only the intercession of all the company saved his head. Once more in charge, Nicuesa governed with an iron fist. His arrogance returned, and his unpopularity grew rapidly. In this yet, unformed colony, he tried to rule like a great monarch of an established kingdom.

Quibián, the native cacique of the area, who had caused so much trouble to the Adelantado, Bartholomew Colon, was still lord of the coast. But he had discovered that famine was a better weapon that his arrows. He got all of natives together and they dug up all of their fields and laid waste to all of the food plants in the area and moved further inland. The Spaniards intent on looking for gold, soon had to give up the search for gold and look for food. All along, with all of the hardships the colony was exposed to, Nicuesa, daily grew more unbearable and treated the survivors very harshly.

With his men dying from sickness and hunger every day, Nicuesa was forced to give up the colony at Belen. They set sail hoping to find somewhere the enterprise would do better and succeed. They sailed along the coast, eastward, when one of the sailors of Columbus's crew told Nicuesa of a beautiful place, Puerto Bello, with an excellent harbor and many springs of potable water. This time, Nicuesa listened to the more experienced sailors When they arrived in Porto Bello, the found, half buried in the sand, an anchor which had been left there by Columbus. But when a party went ashore to fill their water casks they were attacked by Indians. The Spaniards were so weak from exposure and hunger that they could not lift their heavy weapons and were driven back to their boats by the fierce attack. Less than six months had passed since they had sailed so proudly from Española to win and rule a kingdom. Now these old veterans of the Moorish wars had to retreat before a handful of naked savages.

They continued a little farther east along the coast they came to another harbor. The remaining men were so exhausted, that they had hardly enough strength left to navigate. Here, Nicuesa exclaimed, "Paremos aquí en el nombre de Dios!" (Let us stop here in the name of God). The superstitious sailors accepted his words as an omen and they all  disembarked, calling the place "Nombre de Dios." Their bad luck continued, even in this place with a miraculous name. With their last bit of strength, proceeded to built a small fort for the protection from the natives. Once more they were besieged by disease and hunger and men were dying.

Nicuesa had left a few men at the settlement at the Belen River to await the ripening of some corn that they planted. He sent a party he sent to bring them to Nombre de Dios, along with the harvested corn. Instead, they found them so reduced by starvation, and were eating leather to remain alive. 

When he left Española, Nicuesa set sail with two large ships, two brigantines, a caravel, seven hundred men and six horses. His was now reduced to about one hundred, six hundred had already perished, the horses had long since been eaten, and his remaining ships were sinking, victims of the teredo worms, (Sea worms that are the plague of wooden boats. They will bore through the wood and cause the boat to leak, like a sieve).

Nicuesa, and the few who remaining men were reduced to such a sorry shape by diseases and hunger, that they were not able to stand guard duty at night, and were wasting away.

In the middle of November, 1510, the inhabitants of Antigua were surprised one morning to hear the sound of cannons faintly rumbling across the bay from the area of San Sebastian. They at once started great fires with smoke to attract the attention of the ship. They thought that it was Ojeda, returning with reinforcements. How the Enciso, who had been deposed by the colonist, was excited, believing that his position would be restored again. To his disappointment, it turned out to be one of Nicuesa's captains, Rodrigo Enriquez de Colmenares, with a relief expedition for Nicuesa, loaded with provisions and fresh men. 

When he arrived at the settlement, he was given a rousing welcome. With an abundance of provisions, the familiar foods they had been without for such a long time, he was quickly able to established his popularity in Antigua. Hearing of their political dissensions, he urged them to accept Nicuesa as their governor and join forces with him. Colmenares, or anybody from Antigua, was aware of the problems Nicuesa was having at the time. To the men at Antigua, any change seemed like a good idea, and they selected two ambassadors, Diego de Albites and the Bachiller Corral, to accompany Colmenares on his hunt for Nicuesa, to offer him their allegiance and a request that he should come and rule the colony of Antigua.

Colmenares sailed westward along the coast, until he arrived at Nombre de Dios and found Nicuesa and the handful of men that were still alive, now numbered less than one hundred. To Nicuesa, even more grateful than the rescuing ships, was the news that there was a rich and thriving town in his domains which invited him to come and rule over it.

Nicuesa's pride swelled and he at once ordered a feast with the best of Colmenares's provisions. Dressed in new clothes, Nicuesa presiding at the feast. The Spanish wine, which he drank plenty of, went to his head, and he boasted of what he would do in Antigua. He planed to enforce all the fiscal laws and make everyone give an exact account of their booty and confiscate it for himself. He would teach Balboa his place and Zamudio, the other co-mayor. who was a relative of Olano, the man that betrayed him. Colmenares, having spent some time in Antigua, and knowing the disposition of the men there, tried to quiet his master and be careful of what he said. But Nicuesa, after his long bout of  misfortunes, would at least enjoy the glory of talking. The two ambassadors listened to every thing he had to say. They also listen to what the survivors of Nicuesa's expedition said bout him, and became discouraged.

Nicuesa, allowed the ambassadors to return to Antigua, ahead of him. He thought that they would go home and prepare to receive the new governor with much pomp and circumstance.  Instead, they returned to Antigua, and told the colonists was that Nicuesa was going to be a worse tyrant than  Enciso and they should beware. It was a big mistake to allow these ambassadors to go home ahead of him. When he finally left Nombre de Dios, he stopped along the way, taking his time, to attack some of the native villages go get slaves. After taking a long time, he sent Juan de Caicedo to prepare the colony for his planned arrival in August. But Caicedo was not one of his loyal men. When he arrived at Antigua, he proceeded to tell stories of Nicuesa's tyranny and ingratitude. He warned them that Nicuesa would enslave them, steal all of their treasures, and work them like slaves

Dishearten by the news, the depressed colonists, turned to Vasco Nuñez de Balboa for his advice. He advised them that Nicuesa was their lawful governor. Balboa made it a point to have a notary record proceedings and made public acknowledgment of his loyalty to the new governor. He also made it a point to let his friends, out side of the presence of the notary, that it was a mistake to invite Nicuesa to Antigua and that they had to prevent his coming.

When the Governor's ship finally reached the harbor, all the Christians were gathered on the beach. He soon realized that they had not assembled to welcome him but to prevent him from disembarking. The public prosecutor informed him that if he valued his life, he should go back Nombre de Diós. Nicuesa tried to argue his case, but the crowd booed him and made threatening gestures at him. That   night, he was forced to put out to sea, but he returned the next morning. This time, he asked that since they did want him to be their governor, at least let him return as one of them. That he did not want to return to Nombre de Diós. The residents of Antigua argued amongst themselves for some time about if they should allow him to land. After a while, he thought it was safe to land, and no  sooner did he put his foot on land when he was attacked by the crowd. He got away from the mob, because he turned out to be a good runner, and was able to out run his pursuers.

When Nicuesa was eventually captured and brought back to Antigua, he begged that they should keep him as a prisoner, saying that he would rather stay in chains in Antigua, than return to the hell  of Nombre de Dios. But Zamudio, the Alcalde, was committed to Nicuesa's destruction. He forced him and the seventeen followers who were loyal to him, (at this time, there were only 60 men alive out of the seven hundred that started the journey) into the rottenest brigantine of their fleet and forced him to sail back to Española, in March, 1511. After Nicuesa's boat left the harbor of Antigua, it was never heard from or seen again.