About four months after the easy conquest of Goa, the fortune of Albuquerque began to change its appearance, as those persons in Goa on whose fidelity he had reposed most confidence, in spite of the remonstrances of Timoja, entered into plots to deliver up the place to its former master Ismael.  They had submitted so easily to Albuquerque, because unprovided for effectual resistance, to save their properties, and to gain time till Ismael Adel Khan was prepared to come to their relief.  Having at length completed his preparations, he sent on before him in June 1510 his general-in-chief Kamul Khan with 1500 horse and 8000 foot, on which Albuquerque took proper measures to defend his recent acquisition.  Having detected a conspiracy of the Moors to deliver up the city, his first step was to secure and punish the chief conspirators; among these were Mir Cassem and his nephew, to whom he had confided the command of four hundred Moors, whom he caused to be hewed in pieces by his guards; several others were hanged in the most public places of the city, and the rest were rigorously imprisoned, above 100 being convicted of participating in the plot.  By these rigid measures the city was terrified into submission.

Soon afterwards Kamul Khan approached with the van of the army of Ismael, and attempted to pass over into the island by means of boats which he had provided for that purpose.  He was courageously opposed by Noronha, who captured twelve of the boats; many of the enemy were killed by the Portuguese, and many others devoured by the alligators which swarmed in the channel round the island; but at length Kamul Khan effected a landing in force on the island, and the Portuguese were obliged to take refuge within the walls of the city.  Kamul Khan then invested the city with his army, which he began to batter with his cannon, and Albuquerque used every possible effort to defend the place.  Ismael Adel Khan now came up to second his general, at the head of 60,000 men, 5000 of whom were cavalry.  Part of this great army passed over into the island to strengthen the besiegers, and the rest took post in two divisions on the continent to prevent the introduction of provisions, one of these being commanded by an officer of reputation, and the other by the mother and women belonging to Ismael, who maintained their troops by the gain from 4000 prostitutes, who followed the camp.  By the arrival of this vast army the city of Goa was completely surrounded, and no opportunity was left for Albuquerque to execute any enterprise against the numerous assailants.  Making what was necessary prudent, he and his officers resolved to abandon the city before day, which was accordingly executed though with much hazard, the way being occupied by the troops of the enemy, and Albuquerque had his horse killed under him; yet he got off all his men without loss after a siege of twenty days.