King Chairachathirat of the Ayutthaya Kingdom invaded Vientiane with a large army in 1540, captured Muang Khouk and crossed the Mekong, but succumbed to a rout at the battle of Sala Kham, the remnants fleeing for their lives and leaving enormous casualties behind.

Tabinshwehti asked Phothisarath to attack Ayutthaya from the North which eventually resulted in the famous death of Suriyothai in defense of her husband.

In 1527, Phothisarath issued a decree proscribing the worship of animism as groundless superstition, and ordering their shrines to be destroyed and their altars thrown into the river.

[1] He resided much of the time not in the capital at Luang Prabang but in Vientiane, which was located farther south and maintained better communications with the major states of the region.

When Phothisarath died the following year, after a fatal accident while hunting wild elephants, Setthathirath succeeded him and joined together the two kingdoms—which were soon embroiled in Burmese–Siamese wars that would devastate much of the region over the next half-century.