 De' Medici was raised to the cardinalate by Pope Paul V in the consistory of 2 December 1615 and was made Cardinal Deacon of "Santa Maria in Domnica".He was an elector at the papal conclaves of 1621 and 1623 that elected Pope Gregory XV and Pope Urban VIII.He transferred deaconries to that of "San Nicola in Carcere" in 1623, and was the Cardinal protodeacon at the conclave of 1644 that elected Pope Innocent X.