The 72-year-old died in hospital, according to the HINA agency quoting a source close to Praljak, after he drank from a brown bottle at his appeal judgement at the International Criminal Tribunal for the former Yugoslavia (ICTY) in The Hague.
UN judges were handing down judgement in the appeals case of six former Bosnian Croat political and military leaders, in the court's final verdict for war crimes committed during the bloody 1990s break-up of Yugoslavia.
Seconds after his sentence was upheld, the former military commander shouted out angrily: "Praljak is not a criminal. I reject your verdict."
He then drank from the bottle in full view of the cameras filming the hearing, which was quickly suspended as Praljak's lawyer shouted out: "My client says he has taken poison."
Praljak was specifically charged with ordering the destruction of Mostar's iconic Ottoman-era bridge in November 1993, which became symbolic of Bosnia's devastation in the war. The landmark was later rebuilt.
Judges in the first trial had said its destruction over the Neretva river had "caused disproportionate damage to the Muslim civilian population".
But in Wednesday's ruling, judges in fact allowed part of Praljak's appeal, saying the bridge had been a legitimate military target during the conflict. They also overturned some of his convictions, but refused to reduce his overall two-decade sentence.
"Courtroom one is now a crime scene," presiding judge Carmel Agius said as the appeals hearing resumed following the drama.
He gave no other details of the morning's incident, only to say that Praljak was now absent from the courtroom and that on his instructions the Dutch have already started an investigation.