US Republicans failed spectacularly yesterday in their latest effort to dismantle Obamacare, leaving the party shocked and in disarray and signalling the potential death knell for President Donald Trump's dream of repealing his predecessor's health reforms.

The vote -- held in the dead of night -- came down to the wire, with the decisive moment resting with Senator John McCain, recently diagnosed with brain cancer, who sided with two moderate Republicans and all Democrats in opposing the legislation.

"This was a disappointment, a disappointment indeed," Senate Majority Leader Mitch McConnell told colleagues after one of the most tense votes in years on the Senate floor.

"I regret that our efforts were simply not enough this time."

The collapse marks a major setback for Republican leadership and for Trump, who had campaigned relentlessly on a pledge to repeal and replace the Affordable Care Act that passed into law under his predecessor Barack Obama in 2010.

Yesterday's vote, which capped a series of failed efforts in recent months to get an Obamacare repeal measure over the line, was on a so-called "skinny repeal" bill that would have rolled back only parts of Obamacare but kept the bulk of the law intact.

It crashed to defeat, 49-51, leaving Trump's singular legislative initiative, and Republicans' seven-year pledge to rip out the health care law, in tatters.

Trump swiftly spoke out about the failure, apparently unmoved by Democratic pleas for the parties to work together and improve the existing law.

"3 Republicans and 48 Democrats let the American people down," Trump tweeted. "As I said from the beginning, let ObamaCare implode, then deal."

Senate leadership had never intended "skinny repeal" to become law; they saw it as merely a vehicle for joining forces with House Republicans to craft a broader repeal-and-replace plan.

But some Republicans including McCain blasted the bill as terrible policy, and grew nervous that the House of Representatives might turn around and pass the bill instead of going to conference with the Senate.