He commanded the Order during Sultan Suleiman's long and bloody Siege of Rhodes in 1522, when 600 knights and 4500 soldiers resisted an invading force of about 100,000 men for six months, but eventually negotiated the capitulation and the departure of the knights on New Year's Day 1523 to Crete. Villiers de L'Isle-Adam died in Malta on 21 August 1534.