Finally the Empire of Nicaea returned Didymoteicho to Byzantine control by capturing it around 1243, during the reign of John III Doukas Vatatzes. In 1255/56, Theodore II Laskaris used the city as a base of operations for his campaigns against Bulgaria. The city was once again the centre of military operations in 1306, when Michael IX Palaiologos campaigned against the Catalan Company, and again during the Byzantine civil war of 1321–1328 between Andronikos II Palaiologos() and his grandson, Andronikos III (). The latter made Didymoteicho his main base and residence during the conflict, and the city remained a stronghold and was frequently visited by Andronikos III during his reign. The city also served as a secure place of exile and incarceration of the emperor's opponents, from his uncle Constantine Palaiologos in 1322 to the disgraced chief minister Theodore Metochites in 1328.