Mr Kennedy, 76, flew to Washington from his Boston home to back a key bill concerning the US Medicare system.
He arrived in the Senate to a standing ovation from both sides of the chamber.
The bill - to cancel a pay cut for doctors treating Medicare patients - passed by 69 votes to 30. President Bush has threatened to veto it.
Arriving in the Senate chamber to sustained applause from Democrats and Republicans, Mr Kennedy eventually steadied himself to raise his hand and pronounce a loud "Aye" in favour of the bill.
There were loud cheers from the public gallery as he cast his vote.
If the BBC tried to reduce this all to political theater, then at least it was political theater at its best. The state of health care in the United States continues to be, at best, pathetic; and even the slightest efforts at reform always come under siege. Kennedy took this bill seriously and wanted the rest of us to know it:
Win, lose or draw, I wanted to be here. I wasn't going to take the chance that my vote could make the difference.
This makes quite a contrast to the presumptive nominee from Kennedy's own political party, who seemed to think that fighting the best possible battle for that nomination was more important than representing his constituency. Yes, Kennedy was putting on a show; but that does not negate the significance that the show was about something that mattered. These days, I am trying to figure out what really matters to Barack Obama (just as I would like to know his vote on this Medicare bill)!