 Upon his return to the grand duchy in 1641, he resumed the reins of Sienese government.He did not stay long, nevertheless, as the Wars of Castro broke out.Ferdinando II vested in him supreme authority over the grand duchy's military affairs, and thus he commanded the league of the Republic of Venice, the Grand Duchy of Tuscany, the Duchy of Parma and the Duchy of Modena and Reggio against the Barberini Pope, entrusting the government of Siena to his brother Cardinal Leopoldo de' Medici for the duration of his absence.