In the years after his ordination, events again called Jerome to a decision and a new lifestyle. Plague and famine swept northern Italy. Jerome began caring for the sick and feeding the hungry at his own expense. While serving the sick and the poor, he soon resolved to devote himself and his property solely to others, particularly to abandoned children. He founded three orphanages, a shelter for penitent prostitutes and a hospital.
Around 1532 Jerome and two other priests established a congregation dedicated to the care of orphans and the education of youth. Jerome died in 1537 from a disease he caught while tending the sick. He was canonized in 1767. In 1928 Pius Xl named him the patron of orphans and abandoned children.