Sen. John McCain John Sidney McCainBiden's six best bets in 2016 Trump states Replacing Justice Ginsburg could depend on Arizona's next senator The Hill's Morning Report - Sponsored by Facebook - Washington on edge amid SCOTUS vacancy MORE (R-Ariz.) cast the crucial surprise vote that killed Senate Republicans' last-resort ObamaCare repeal bill early Friday morning in a shocking moment that at least temporarily ended the GOP's hopes of eliminating the former president's signature law.

Voting shortly after midnight, McCain — who returned to the Senate on Tuesday after being diagnosed with brain cancer the week before — joined GOP Sens. Susan Collins Susan Margaret CollinsGraham: GOP will confirm Trump's Supreme Court nominee before the election Gardner signals support for taking up Supreme Court nominee this year Tumultuous court battle upends fight for Senate MORE (Maine) and Lisa Murkowski Lisa Ann MurkowskiGraham: GOP will confirm Trump's Supreme Court nominee before the election Gardner signals support for taking up Supreme Court nominee this year Tumultuous court battle upends fight for Senate MORE (Alaska) and all Democrats in opposing the measure that would have repealed key parts of ObamaCare.

McCain cast the no vote two days after a dramatic return to the Senate floor during which he called on his colleagues to work together on major issues, which has long been a Senate tradition until the upsurge of partisanship in recent years.

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The vote cements McCain's status as the Senate's maverick, a role he relished earlier in his career when President George W. Bush occupied the White House.

McCain, who was defeated in the 2008 presidential election that brought Barack Obama Barack Hussein ObamaTwitter investigating automated image previews over apparent algorithmic bias Donald Trump delivers promise for less interventions in foreign policy Rush Limbaugh encourages Senate to skip hearings for Trump's SCOTUS nominee MORE to power, has emerged this year as one of President Trump’s most outspoken critics in Congress.

The two feuded during Trump's presidential campaign; at one point, Trump mocked McCain for being a prisoner of war, saying he liked war heroes who were not captured.

That history simply added to the drama of Friday morning's vote.

The bare-bones healthcare proposal, dubbed the “skinny” repeal because it left untouched big sections of ObamaCare, would have resulted in 16 more million people being without insurance over a decade, according to the Congressional Budget Office.

The CBO also estimated that it would increase premiums by 20 percent compared to current law.

Given those statistics, there was speculation early in the week about whether McCain would vote with his party given his own health news.

McCain did vote with Republicans to start debate on Tuesday but warned he was opposed to the current version of their repeal-and-replace legislation.

He further warned on Thursday that he did not want the skinny bill to become law and asked for assurances from Speaker Paul Ryan Paul Davis RyanKenosha will be a good bellwether in 2020 At indoor rally, Pence says election runs through Wisconsin Juan Williams: Breaking down the debates MORE (R-Wis.) that there would be a conference and that the House would not just pick up the skinny bill and pass it.

Other senators aligned with him seemed reassured by a Ryan statement and backed the skinny bill. But McCain appeared to feel differently with his own vote.

Senate Majority Leader Mitch McConnell Addison (Mitch) Mitchell McConnellGraham: GOP will confirm Trump's Supreme Court nominee before the election Trump puts Supreme Court fight at center of Ohio rally The Memo: Dems face balancing act on SCOTUS fight MORE (R-Ky.) pushed the skinny bill as a backup proposal after Republicans failed to agree on a bigger bill that repealed and replaced the pillars of ObamaCare or on a repeal-only measure that passed both chambers in 2015.

He appeared almost distraught after McCain’s surprise vote and seemed close to choking up on the floor after falling short of his promise to repeal ObamaCare.

“This is clearly a disappointing moment,” he said.

“I regret that our efforts were simply not enough this time. Now, I imagine many of our colleagues on the other side are celebrating. Probably pretty happy about all this. But the American people are hurting, and they need relief.”

Many Republican senators, however, did not support the substance of the skinny legislation. They decided to vote for it as a way to prolong the healthcare negotiation by setting up a conference negotiation with the House.

Still, McCain’s vote surprised many Republicans, including Sen. Bill Cassidy (La.), who said he thought the Arizona Republican was in favor of the legislation.

Sen. Ron Johnson Ronald (Ron) Harold JohnsonThis week: Supreme Court fight over Ginsburg's seat upends Congress's agenda GOP set to release controversial Biden report Democrats fear Russia interference could spoil bid to retake Senate MORE (R-Wis.) told reporters, “I’m shocked at this.”

Vice President Pence was spotted lobbying McCain on the Senate floor shortly before the crucial vote. He also worked on Collins while other GOP leaders focused on Murkowski.

But those efforts fell short.

Senate Republican Conference Chairman John Thune John Randolph ThuneGraham: GOP will confirm Trump's Supreme Court nominee before the election Tumultuous court battle upends fight for Senate What Senate Republicans have said about election-year Supreme Court vacancies MORE (R-S.D.) said McCain was wrestling with the decision all day but in the end would not budge.

“He had made up his mind and I’m not sure there was much that could have been done about it,” he said.

McCain declined to outline his thought process when reporters asked him about his vote.

Whatever he may have thought about, the diagnosis of brain cancer he received from doctors last week hovered over his decision.

None of his colleagues mentioned it explicitly, but many Democrats thought it would be a sad irony if the lawmaker voted for legislation the CBO projected would cause 16 million more people to be without health insurance at a time when he was depending on doctors in his fight against cancer.

In addition, McCain was never a big fan of the Senate healthcare reform effort, which would have cut billions of dollars in Medicaid funding for his home state of Arizona, one of 30 states that expanded enrollment under ObamaCare.

He raised Republican suspicions and Democratic hopes shortly before the vote when he declined to tell reporters how he would vote on the latest idea from the GOP leadership, the skinny repeal.

One Republican leadership source predicted earlier in the day that it had a “nine out of 10” chance of passing.

But McCain’s defection became apparent when he began huddling with Democrats on the Senate floor.

He complained earlier this month after Senate GOP leaders left out three Medicaid-related amendments that Arizona Gov. Doug Ducey (R) asked to be included in the bill.

McCain joined Johnson, Cassidy and Sen. Lindsey Graham Lindsey Olin GrahamGraham: GOP will confirm Trump's Supreme Court nominee before the election Fox's Napolitano: Supreme Court confirmation hearings will be 'World War III of political battles' Grassley, Ernst pledge to 'evaluate' Trump's Supreme Court nominee MORE (R-S.C.) at a press conference a few hours before the vote, during which they asked for assurances from House GOP leaders that the skinny bill would be revised substantially in a conference negotiation with the House.

Ryan tried to provide some assurance by telling senators that he was willing to work with them, but a Ryan spokesperson earlier in the day described a conference negotiation as an “option” but not a certainty.

“If moving forward requires a conference committee, that is something the House is willing to do,” Ryan said in a statement.

But McCain told reporters that pledge did not go far enough.

“I would like to have the kind of assurances he did not provide,” he said.

Updated at 7:12 a.m. Jordain Carney, Rachel Roubein and Peter Sullivan contributed.