Slobodan Praljak, 72, died in hospital, with the UN court announcing that the courtroom was now "a crime scene".
On hearing that his 20-year jail term had been upheld, the ex-commander of Bosnian Croat forces said he was not a criminal and then drank from a bottle.
In 2013, he was sentenced for crimes in the city of Mostar during the Bosnian war from 1992-95.
Praljak was one of six former Bosnian Croat political and military leaders up before the International Criminal Tribunal for the former Yugoslavia (ICTY).
They were attending the final appeals judgment to be handed down by the court.
Though allies against the Bosnian Serbs in the war, Bosnian Croats and Muslims also fought each other for a period of 11 months, with Mostar seeing some of the fiercest fighting.