 He was briefly Cardinal Deacon of "Sant'Eustachio", before being raised to the order of Cardinal Priests in December 1644, with the title of "San Sisto".The next year, de' Medici was raised to Cardinal Bishop of Sabina, but opted for the suburbicarian see of Frascati seven months later.On 29 April 1652 he was made Cardinal Bishop of Porto e Santa Rufina and Vice-Dean of the College of Cardinals.