Emperor Leo VI the Wise retrieved him from the monastery and made him mystikos, a dignity designating either the imperial secretary or a judicial official.

This unpopular concession undermined his position, and by March 914, with the support of the magistros John Eladas, Zoe Karbonopsina overthrew Nicholas I and replaced him as foremost regent.

With her main supporter Leo Phokas the Elder crushingly defeated by the Bulgarians at the battle of Achelous in 917, Zoe started to lose ground.

Embarrassed by further failures, she and her supporters were supplanted in 919 by the admiral Romanos Lekapenos, who married his daughter Helena Lekapene to Constantine VII and finally advanced to the imperial throne in 920.

In addition to his numerous letters to various notables and foreign rulers (including Simeon I of Bulgaria), Nicholas Mystikos wrote a homily on the sack of Thessalonica by the Arabs in 904.