In early 1568, the captive Siamese king, Maha Chakkraphat, who had become a monk, successfully convinced Bayinnaung to allow him to go back to Ayutthaya on pilgrimage. Upon his arrival, in May 1568, he disrobed and revolted. He also entered into an alliance with Setthathirath of Lan Xang. On 30 May 1568, a dismayed Bayinnaung sent an army of 6,000 to reinforce the defences at Phitsanulok, whose ruler had remained loyal to him. Phitsanulok withstood the siege by joint Siamese and Lan Xang forces till October when the besiegers withdrew to avoid what was to come. On 27 November 1568, 55,000-strong Burmese armies arrived at Phitsanulok. Reinforced at Phitsanulok, combined armies of 70,000 marched down to Ayutthaya, and laid siege to the city in December 1568. A month into the siege, Maha Chakkraphat died, and was succeeded by Mahin in January 1564. Setthathirath tried to break the siege but his army was severely defeated northeast of the city on 23 April 1569. Mahin finally offered to surrender but the offer was not accepted. The city finally fell on 8 August 1569. Bayinnaung appointed Maha Thammaracha, the viceroy of Phitsanulok, as vassal king on 30 September 1569. The Burmese rule would not be challenged for another 15 years, until after Bayinnaung's death.

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