Mr. Holbrooke experienced health problems in August, when he underwent treatment for heart problems and canceled one of his frequent trips to Afghanistan and Pakistan.
On Friday morning, he was taken to George Washington University Hospital after he became flushed and suffered chest pains during a meeting with Clinton.
He underwent a 21-hour operation that ended on Saturday to repair his aorta.
As Mr. Holbrooke was sedated for surgery, family members said, his final words were to his Pakistani surgeon: "You've got to stop this war in Afghanistan.
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