Branas held the new emperor Isaac II Angelos in contempt, this, combined with his successes as a general and connections to the former imperial dynasty of the Komnenoi, emboldened him to aspire to the throne.

In 1187, Branas was sent to counter the Vlach-Bulgarian Rebellion and Niketas Choniates praised him for his deeds against the rebels. This time, in contrast to his loyalty to Andronikos I, he did rebel; he was proclaimed emperor in his native city of Adrianople, where he mustered his troops and gained the backing of his kinsmen. Branas then advanced on Constantinople, where his troops gained an initial success against the defending army. However, he was unable to pierce or bypass by the city's defences, or suborn the defenders, and could not gain entry by any means. The imperial forces led by Conrad of Montferrat, the emperor's brother-in-law, made a sortie. The troops of Branas began to give way under pressure from Conrad's heavily equipped infantry. In response Branas personally attacked Conrad, but his lance thrust did little harm. Conrad then unhorsed Branas, his lance striking the cheekpiece of Branas' helmet. Once on the ground, Alexios Branas was beheaded by Conrad's supporting footsoldiers. With their leader dead, the rebel army fled the field. Branas' head was taken to the imperial palace, where it was treated like a football, and was then sent to his wife Anna, who (according to the historian Niketas Choniates) reacted bravely to the shocking sight.