[4] In 1528, Vadillo and Heredia landed in Santa Marta with 200 men and soon became involved in disputes with Rodrigo Alvarez Palomino, a former lieutenant of Bastidas, which were resolved when the latter was drowned in the river that bears his name.

Vadillo served as interim governor of Santa Marta but returned to Santo Domingo to face a residencia (an administrative and judicial tribunal).

Once in Madrid, Heredia initiated efforts to gain royal approval to secure the conquest and government of the Bay of Cartagena and New Andalucía, a territory that stretched from the mouth of the Magdalena River to Darién Province, which had belonged to Alonso de Ojeda.

[5] Heredia first landed in Puerto Rico, where he found the survivors of an expedition led by Sebastian Cabot, who was on his way back from the Rio de La Plata after six difficult and unsuccessful years spent in the New World.

[6] After spending Christmas Day in Santo Domingo, Heredia sailed across the Caribbean Sea to the mainland of South America where he cruised off the coast into Santa Marta Bay and then past the mouth of the Magdalena River.

[7] He passed several villages of the Mokaná Indians, until on January 14, 1533 he reached Calamari, the largest of them, standing on the sandy inner shore of Cartagena Bay.

[10] Pedro de Heredia prepared a second expedition to the South Sea and in 1534 he reached the Sinú river, where he ransacked the indigenous peoples' tombs for gold.

Once there, Heredia met Fray Tomas de Toro, the first bishop of Cartagena, sent by king Carlos I of Spain, and his brother Alonso, who had recently arrived from Guatemala.

He returned to Cartagena with some members of his family: a few nieces and his two sons, Antonio, who joined him on all his subsequent expeditions, and Juan, who later settled in Santa Cruz de Mompox.

The visitador (a royal inspector who reported to the Council of the Indies) Miguel Diez de Armendáriz found him guilty of all charges; Heredia, however, continued to hold his administrative position.

The accusations included: illegal appropriation of royal funds, nepotism, obstruction of municipal chapter deliberations, severe abuses directed toward the native population such as burning alive, mutilations and torture.

[18] On January 27, 1554, (some sources say 1555)[19][20] his ship La Capitana, part of Cosme Farfán's fleet, sank off the coast of Zahara de los Atunes.