In the absence of his relative, King Simon I of Kartli, in the captivity in Safavid Iran, Vakhtang was installed by the nobility as a regent in opposition to the pro-Safavid regime of Daud-Khan from 1569 to 1579.
One of brothers, Archil, was captured by the Iranian military in 1557 and another, Ashotan, was killed when the mountaineers of Pkhovi raided Mukhrani in 1561.
After Daud-Khan burned down his capital, Tbilisi, before abandoning it to the Ottoman army under Lala Kara Mustafa Pasha, Vakhtang, as a regent of Kartli, sent Bardzim, Prince Amilakhvari, and Elizbar, Duke of Ksani, to come to common terms with the victor, saving, as the 18th-century historian Prince Vakhushti put it, "the people from annihilation".
[3][1][4] In October 1578, Simon I, released by the shah from captivity, returned to Kartli and struck at the Ottoman garrisons as well as his old foes.
He died shortly thereafter, in 1580, being succeeded as Prince of Mukhrani by his son, Teimuraz I, under the regency of Vakhtang's nephew Erekle I.