Several emergency rescue workers rushed into the building carrying equipment in backpacks, while court officials called for calm.
Croatia's state-run TV service later said he died in hospital in the Netherlands, a statement which was later confirmed by Prime Minister Andrej Plenković, who offered condolences to his family.
Plenkovic said at a press conference that "we have all unfortunately witnessed his act by which he took his own life".
"His act mostly speaks about a deep moral injustice towards six Croats from Bosnia and the Croatian people ... We voice dissatisfaction and regret about the verdict."
Judge Agius declared the courtroom to be a crime scene as he restarted the hearing, though gave no further details.
Dutch police also said an investigation had been launched, but would not disclose whether Praljak was alive or dead.
Praljak was sentenced to 20 years in jail along with his co-conspirators back in 2013, though it is not clear if he began serving that sentence before his appeal.
Bosnian Croats and Muslims were allies against the Serbs but fought each other for 11 months from 1993-1994.
Praljak, a Croatian politician and general in the the Croatian Army, also commanded Bosnian Croat forces known as the HVO from July to November 1993.
During this time, Praljak and his allies were trying to establish the "Croatian Republic of Herzeg-Bosnia" - an ethnically Croatian enclave, with the city of Mostar as it's "capital".
The Herzeg-Bosnia republic was declared by the Bosnian Croats in 1993, but as part of the peace agreement in 1994, it merged with the Federation of Bosnia and Herzegovina that we know today.
Mostar saw the worst of the Croat-Muslim clashes, with nearly 80 per cent of the city's east destroyed in the fighting.
Praljak was specifically charged with ordering the destruction of Mostar's 16th-century bridge in November 1993, which judges in the first trial had said "caused disproportionate damage to the Muslim civilian population".
A symbol of Bosnia's devastation in the war, the Ottoman-era bridge was later rebuilt.
But in their ruling, the judges in fact allowed part of Praljak's appeal, saying the bridge had been a legitimate military target during the conflict.
"It's just an old bridge," Praljak said in 1993, showing no regard for the emotional effect the destruction had on ordinary Bosnians of all ethnic backgrounds.
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