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On 23 May 1480 an Ottoman fleet of 160 ships appeared before Rhodes, at the gulf of Trianda, along with an army of 70,000 men under the command of Gedik Ahmed Pasha or Mesih Pasha. The Knights Hospitaller garrison was led by Grand Master Pierre d'Aubusson. The Knights were reinforced from France by 500 knights and 2,000 soldiers under d'Aubusson's brother Antoine.<br/><br/>

The Ottomans first strategic goal was to capture the Tower of St Nicholas, which was the knights key-point in the defence of the two harbours: the commercial, Mandraki, and the one to the east bay of Akandia. The Turkish artillery kept up an unbroken bombardment and on 9 June the infantry made a series of attacks. Grand Master d'Aubusson himself sped to the aid of the garrison and after a fierce struggle the enemy was repelled.<br/><br/>

Shortly after came a second attack on the tower, this time on the eastern sector of the wall towards the bay of Akandia, which was the battle station of the 'tongue' of Italy and was quite weak. During the bombardment from the Turkish artillery, the Knights and the people meanwhile dug a new moat on the inside of the wall at this point and constructed a new internal fortification. Once again the Knights reacted valiantly and decisively and after a bitter battle with many casualties on both sides, the danger was once more averted.<br/><br/>

The last act of the drama was played out in the Jewish quarter of the city. At dawn on 27 July the Turks launched a vigorous offensive and their vanguard of around 2,500 janissaries managed to take the tower of Italy and enter the city. A frenzied struggle ensued. The grand master, wounded in five places, directed the battle and fought with lance in hand. After three hours of fighting the Turks were decimated and the exhausted survivors began to withdraw.
The Siege of Rhodes of 1522 was the second and ultimately successful attempt by the Ottoman Empire to expel the Knights of Rhodes from their Greek island stronghold and thereby secure Ottoman control of the Eastern Mediterranean. The first siege, in 1480, had been unsuccessful.<br/><br/>

The Knights of St. John had captured Rhodes in the early 14th century after the loss of Acre, the last Crusader stronghold in Palestine in 1291.<br/><br/>

When the Turkish invasion force of 400 ships arrived on Rhodes on 26 June 1522, they were commanded by Mustafa Pasha. Sultan Suleiman himself arrived with the army of 100,000 men on 28 July to take personal charge. The Turks blockaded the harbor and bombarded the town with field artillery from the land side, followed by almost daily infantry attacks. They also sought to undermine the fortifications through tunnels and mines.<br/><br/>

On 24 September, Mustafa Pasha ordered a new massive assault, aimed mainly at the bastions of Spain, England, Provence and Italy. After a day of furious fighting, during which the bastion of Spain changed hands twice, Suleiman eventually called off the attack. He sentenced Mustafa Pasha, his brother-in-law, to death for his failure to take the city, but eventually spared his life after other senior officials had pleaded with him for mercy. Another major assault at the end of November was repelled, but both sides were now exhausted—the Knights because they were reaching the end of their capacity to resist and no relief forces could be expected to arrive in time.<br/><br/>

On 22 December, the representatives of the city's Latin and Greek inhabitants accepted Suleiman's terms, which were surprisingly generous. The knights were given 12 days to leave the island and would be allowed to take with them their weapons and any valuables or religious icons they desired. Islanders who wished to leave could do so at any time within a three-year period. No church would be desecrated or turned into a mosque. Those remaining on the island would be free of Ottoman taxation for five years.<br/><br/>

On 1 January 1523, with much fanfare, the remaining knights and soldiers marched out of the town with banners flying, drums beating and in battle armour. They boarded the 50 ships which had been made available to them and sailed to Crete (a Venetian possession), accompanied by several thousand civilians.