Richard Holbrooke, the US envoy to Afghanistan and Pakistan, has been taken critically ill, the US state department says.
Mr Holbrooke, 69, was admitted to hospital on Friday and has undergone surgery to repair a tear in his aorta.
His family have joined him at his hospital bedside in Washington DC.
Mr Holbrooke is best known for brokering the Dayton peace accords in 1995, which ended the Bosnian war.
President Barack Obama named Mr Holbrooke as his special representative to Afghanistan and Pakistan in January 2009.
Since then, he has played a key role in defining the strategy for the Obama administration on one of its foreign policy priorities.
Mr Obama said he and his wife Michelle were praying for Mr Hobrooke, describing him as a "tireless public servant" and a "towering figure in American foreign policy".
"We continue to pray for his recovery, and support his family in this difficult time," Mr Obama said.
Mr Holbrooke was working at the State Department when he was taken ill.
In a brief statement released on Saturday, State Department spokesman PJ Crowley said: "This morning, doctors completed surgery to repair a tear in his aorta. He is in critical condition and has been joined by his family".
The aorta is the largest artery in the human body and carries oxygenated blood from the heart.
Nicknamed "the Bulldozer", Mr Holbrooke has gained a reputation for confronting warring leaders to get them to come to the negotiating table.
Mr Holbrooke is one of the state department's top diplomats, having served in Vietnam and at the United Nations.
In the wake of his success at Dayton, he was nominated for the Nobel Peace Prize.
In 1997, then President Bill Clinton named him as ambassador to the UN.
In his role as President Obama's envoy, he has clashed regularly with Afghan president Hamid Karzai.
After the disputed presidential elections in August 2009, Mr Holbrooke was widely reported to have confronted Mr Karzai about poll irregularities.
However, a spokeswoman for the US embassy in Kabul denied there had been any shouting or that Mr Holbrooke had stormed out.
Mr Holbrooke was later criticised by US Gen Stanley McChrystal in a controversial article published in Rolling Stone magazine in June.
In the article, Gen McChrystal was quoted as saying: "Oh, not another e-mail from Holbrooke... I don't even want to open it."
As a consequence of his remarks, Gen McChrystal was sacked by President Obama.
Mr Holbrooke has maintained a hectic travel schedule.
In September, he visited Pakistan to see the aftermath of the floods which devastated the country.
He has also travelled to the north-west of the country, a stronghold for insurgents which lies largely outside government control.
Mr Holbrooke was born in New York and is of German-Jewish descent. He was educated at Brown University, and is married to the writer, Kati Marton.
As well as his diplomatic career, Mr Holbrooke has also worked in the financial sector.