Following this service to his Order, Antonini was elevated to the rank of cardinal by Pope Leo X in the consistory of 1 July 1517, and given the titular church of San Bartolomeo all'Isola, which he immediately had changed to the Church of San Matteo in Via Merulana. He resigned the office of Prior General in February 1519. Pope Leo confided to him several sees in succession, employed him as legate on important missions, notably to Charles of Spain, soon to be Emperor. In 1523 Pope Leo gave him the title of Latin Patriarch of Constantinople.