Orsini was Archbishop of Naples from 1400 until 1405, when he was made a Cardinal by Innocent VII. In 1408 he abandoned the "Roman Obedience" and attended the Council of Pisa. He was subsequently administrator of the see of Pécs 1409-10, and legate of Antipope John XXIII in Spain, Picenum and Bologna. Promoted to the suburbicarian see of Albano in 1412, he had a considerable role in the Council of Constance, where he presided over the fifth session. He was the papal legate appointed to establish peace between England and France in 1418. Grand penitentiary from 1419. Legate of Pope Martin V in Bohemia, Hungary and Germany in prosecution of the Hussites in 1426.