US Senate Republicans ha ve failed to dismantle Obamacare, falling short on a major campaign promise and perhaps ending a seven-year quest by their party to gut the healthcare law.

The failure was a stinging blow to President Trump, who campaigned on a promise to repeal the legislation that has seen millions of previously uninsured Americans get coverage. Recent polls show Obama is now favoured by a majority of the population.

The decisive blow was delivered by Senator John McCain, the former presidential candidate mocked by Trumped for being captured and spending years in a Vietnamese POW camp. He suffered lasting disabilities as a result of his experience.

Voting in the early hours of this morning, McCain was one of three Republican senators, with Susan Collins and Lisa Murkowski, to cross party lines and join Democrats in a dramatic 49-to-51 vote to reject a 'skinny repeal' bill that would have killed some parts of Obamacare.

The bill would have removed the individual mandate requiring all Americans to have health insurance or pay a fine. The non-partisan congressional budget committee estimated that 15 million people would lose coverage if it passed and premiums would rise by 20 per cent.

Trump tweeted his disappointment at the outcome, promising to 'let Obamacare implode'.

'This is clearly a disappointing moment,' Senate Republican leader Mitch McConnell said on an eerily quiet Senate floor right after the vote. 'The American people are going to regret that we couldn't find a better way forward.'

The setback leaves Trump without a major legislative win after more than six months in power, despite Republicans controlling the White House, Senate and House. It will also be a let-down for financial markets, which expected Trump to make rapid changes to healthcare, taxes and infrastructure spending.

'3 Republicans and 48 Democrats let the American people down. As I said from the beginning, let Obamacare implode, then deal. Watch!' Trump tweeted after the vote.

Trump has repeatedly berated congressional Republicans for being unable to overcome internal divisions to repeal Obamacare, but has offered no legislation himself, nor any clear guidance on what he would like to do about replacing the law.

The president has demanded at various times that Obamacare should be allowed to collapse on its own, that it should be repealed without replacement, and that it should be repealed and replaced.

The Affordable Care Act, approved by Democrats in 2010, is former Democratic President Barack Obama's signature domestic achievement. It provided health insurance to millions of previously uninsured Americans.

Republicans hold 52 seats in the 100-seat Senate. McConnell, whose reputation as a master legislative tactician was on the line, could only afford to lose support from two Republican senators, with the tie-breaking vote to be cast by Vice President Mike Pence, who was on the Senate floor.

After the vote, the Senate Democratic leader, Chuck Schumer, spoke to reporters about McCain's vote.

He said he and McCain had spoken frequently since the Arizona senator, recently diagnosed with brain cancer, returned to Washington.

'Given his stature, his remarks at the beginning when he came in, moved everybody and I think that helped,' Schumer said. 'He's a hero. He's a hero of mine.'

Additional reporting by Reuters.