Alfonso of Calabria; Petrucci exerted an effective rule on the city until his death in 1512, favouring arts and sciences, and defending it from Cesare Borgia. Pandolfo was succeeded by his son Borghese, who was ousted by his cousin Raffaello, helped by Pope Leo X. The last ruler in the Petrucci Dynasty was Fabio Petrucci|Fabio, who was exiled in 1523 by the Sienese people. Internal strife resumed, with the popular faction ousting the Noveschi party supported by Clement VII: the latter sent an army, but was defeated at Camollia in 1526. Emperor Charles V took advantage of the chaotic situation to put a Spanish garrison in Siena. The citizens expelled it in 1552, allying with France: this was unacceptable for Charles, who sent his general Gian Giacomo Medici to lay siege to it with a Florentine-Imperial army.
The Sienese government entrusted its defence to Piero Strozzi. When the latter was defeated at the Battle of Marciano (August 1554), any hope of relief was lost. After 18 months of resistance, it surrendered to Spain on 17 April 1555, marking the end of the Republic of Siena. The new Spanish King Philip, owing huge sums to the Medici, ceded it (apart a series of coastal fortress annexed to the State of Presidi) to the Grand Duchy of Tuscany, to which it belonged until the Italian unification in the 19th century. A Republican government of 700 Sienese families in Montalcino resisted until 1559.
The picturesque city remains an important cultural centre, especially for humanist disciplines
