The most significant event of his reign was the attack of the Fourth Crusade on Constantinople in 1203, on behalf of Alexios IV Angelos. Alexios III took over the defence of the city, which he mismanaged, and then fled the city at night with one of his three daughters. From Adrianople, and then Mosynopolis, he attempted unsuccessfully to rally his supporters, only to end up a captive of Marquis Boniface of Montferrat.
The most significant event during Alexios III's reign was the Fourth Crusade's assault on Constantinople in 1203, orchestrated by Alexios IV Angelos.  Alexios III took charge of defending the city but failed to do so effectively and fled with one of his daughters at night. He then attempted to rally supporters from Adrianople and Mosynopolis, but ultimately ended up a captive of Marquis Boniface of Montferrat.