In 1571, the Ayutthaya Kingdom and Lan Na were Burmese vassals. Having twice defended Lan Xang from Burmese invasions, King Setthathirath moved south to conduct a campaign against the Khmer Empire. Defeating the Khmer would have greatly strengthened Lan Xang, giving it vital sea access, trade opportunities, and most importantly, European firearms which had been growing use since the early 1500s. The Khmer Chronicles record that armies from Lan Xang invaded in 1571 and 1572, during the second invasion King Barom Reacha I was slain in an elephant duel. The Khmer must have rallied and Lan Xang retreated, Setthathirath went missing near Attapeu. The Burmese and Lao Chronicles record only the presumption that he died in battle.^[40]

Setthathirath's general Sen Soulintha returned to Vientiane with the remnants of the Lan Xang expedition. He fell under immediate suspicion, and a civil war raged in Vientiane as a succession dispute took place. In 1573, he emerged as king regent but lacked support. Upon hearing reports of the unrest, Bayinnaung dispatched emissaries demanding the immediate surrender of Lan Xang. Sen Soulintha had the emissaries killed.^[41]

Bayinnaung invaded Vientiane in 1574, Sen Soulintha ordered the city to be evacuated but he lacked the support of the people and the army. Vientiane fell to the Burmese. Sen Soulintha was sent as a captive to Burma along with Setthathirath's heir Prince Nokeo Koumane.^[42] A Burmese vassal, Chao Tha Heua, was left to administer Vientiane, but he would rule only four years. The First Taungoo Empire (1510–99) was established but faced internal rebellions. In 1580 Sen Soulintha returned as a Burmese vassal, and in 1581 Bayinnaung died with his son King Nanda Bayin in control of the Toungoo Empire. From 1583 to 1591 a civil war took place in Lan Xang.^[43]