To assist and succeed him in church affairs, Clement VII created his cousin Ippolito a cardinal on 10 January 1529, and on the same day named him first Archbishop of Avignon, a position that brought him a considerable income.

[7] On 15 February 1530, Pope Clement granted Cardinal Ippolito a ⅓ share in the annual papal income from the town and territory of Chiusi for his lifetime.

[8] Ippolito was sent to Hungary in the spring of 1532 as Papal Legate,[9] departing from Rome on 8 July, according to the diaries of the Italian literatus Pietro Aretino.

[citation needed] By 24 April 1531, Catherine had been promised to Henry, the son of King Francis I of France, in a draft contract of marriage.

In 1535, free of his cousin's influence, Cardinal Ippolito acted as Florentine ambassador to Emperor Charles V, happily conveying complaints against the administration of Alessandro de' Medici.

He is reported as having a troupe of so-called Savages, speaking over twenty languages; there were also Moors, Tartars, Indians, Turks and Africans.