He was created cardinal deacon in the consistory of 14 December 1588 under Pope Sixtus V, and received the deaconry of S. Maria in Domnica the following year. He took part in the two conclaves of 1590 (Papal Conclave of September 1590 and the Papal Conclave of Autumn 1590), the conclave of 1591 and the conclave of 1592. He subsequently took the titles of Santa Maria in Aracoeli, Santa Maria in Trastevere, and S. Lorenzo in Lucina. As a cardinal he proved an accomplished diplomat and administrator: he represented the interests of the Grand Duke of Tuscany, the former Cardinal Ferdinando de' Medici, in Rome, and was firmly but discreetly pro-French in the ongoing struggle between the French and Spanish for influence over the papacy.