Bill Cassidy pulled back from a political gamble four years ago. Now he's taken the riskiest bet of his career.

The second-term senator shocked his colleagues and Louisiana Republicans by voting to move forward with President Donald Trump’s impeachment trial as he trashed Trump’s legal team for doing a “terrible job" in its opening argument. While few of his colleagues would criticize Cassidy directly, the Louisiana GOP immediately said it was “profoundly disappointed” in him and praised his colleague, Sen. John Kennedy (R-La.), for making the “right decision.”

Not long after, the local party in his hometown of Baton Rouge said Cassidy’s vote “was a betrayal of the people of Louisiana and a rebuke to those who supported President Trump.” It censured Cassidy and “holds him out as an object of shame.” One Louisiana Republican official expected more such condemnations to come.

“Republican voters realize this is not healing, it’s not unifying, it’s vindictive and divisive. And they’d prefer we move on,” said Sen. Ron Johnson (R-Wis.). He said Cassidy’s move surprised him: “That’s his decision and he has to evaluate what he’s doing.”

Cassidy, a doctor who treated uninsured patients for years in the state’s charity health care system, evaded easy typecasting during the Trump era. He’s not a loyalist like Lindsey Graham or Rand Paul. Nor is he a frequent critic of the ex-president like Mitt Romney or Bob Corker. But he's a reliable conservative vote, close to party leaders.

On Wednesday, Louisiana local radio host Moon Griffon heard from callers frustrated with “Psycho Bill” and said Cassidy “just knifed us all in the back.” Cassidy explained his thinking on Wednesday as his position came under scrutiny: “It is Constitution and country over party. For some, they get it. And others aren’t quite so sure.”

“I don't usually do a poll before I take my vote. The vote I took is the conservative constitutional position,” he said.

He was subsequently praised by former Sen. Mary Landrieu (D-La.): "Many people in Louisiana are proud of him, including me." But Cassidy’s experience this week is a sign of what’s to come for Republicans who vote to convict the president in the coming days.

Of the six GOP senators to support moving forward with the trial, only Sen. Lisa Murkowski (R-Alaska) will face voters next year — and she’s won re-election after losing her primary before. Cassidy just won a six-year term himself.

“It’s fraught with political consequence,” said Sen. John Thune (R-S.D.), the GOP whip. Thune faced retribution from Trump simply for opposing the former president’s efforts to overturn the election. He voted to find the trial unconstitutional but said the vivid presentation of videos of the Capitol insurrection was effective by House impeachment managers.

In fact on the most important question thus far, 44 GOP senators sided with Trump, a healthy margin that signals Trump may still easily avoid conviction and the possibility of being barred from running again in 2024. Republicans said there were few signs that others would follow Cassidy’s lead and defect from the president’s side when it comes down to the final vote.

“If you don’t think there’s jurisdiction, I don’t know how you vote to convict,” said Sen. Josh Hawley (R-Mo.), a constitutional lawyer who challenged some state’s election results last month.

In 2017, Cassidy was a leading player in the party’s efforts to repeal the Affordable Care Act. Cassidy initially pushed his party to pass the so-called “Jimmy Kimmel” test and not deny coverage for pre-existing conditions. That alliance with the talk show host ended with Kimmel calling Cassidy a liar and asserting he abandoned his commitment. But Cassidy stayed in Trump’s good graces as he worked with the president on health care reform, though the party’s effort eventually sputtered.

“You are doing an outstanding job representing the people of Louisiana & the U.S.A. You have my Complete and Total Endorsement!” Trump tweeted in March, endorsing Cassidy. The senator won reelection by 40 points in November.

Trump probably doesn’t feel that way these days, though it’s been more difficult to tell if Trump is angry at GOP senators after his Twitter account was shut down. But Trump’s followers are doing much of the work for him.

There’s a clear undercurrent in the party to punish Republicans who cross the president, in either his trial in the Senate or on the impeachment articles in the House. Rep. Liz Cheney (R-Wyo.) was censured by her state party, Sen. Ben Sasse (R-Neb.) is facing similar punishment, and Cassidy is now in his party’s bad graces.

“I’ve been doing a lot of phone calls to donors. Most people that I talk to have moved on,” said National Republican Senatorial Committee Chairman Rick Scott (R-Fla.) about Trump’s trial.

Rep. Mike Johnson (R-La.) said he was receiving lots of calls about Cassidy’s vote — though that will likely die down if Cassidy votes to acquit Trump. Cassidy hasn’t signaled where he will fall on the final trial vote, but his acknowledgment that the House managers convinced him that the trial was constitutional suggests he is persuadable.

“This does not predict my vote or anything else,” Cassidy told reporters on Wednesday. “It does predict that I will listen to these arguments as I did to the arguments yesterday, with an open mind.”

Meanwhile, he has some defenders back home. "The real offense some folks are seeking to punish is that Sen. Cassidy is acting insufficiently loyal to one man. One man. And if that’s the case, it strikes me as the opposite of what it means to be a Republican," said Michael DiResto, a member of Louisiana's Republican State Central Committee.

Generally an ally for GOP leaders in both the House and Senate, Cassidy has shown a desire for a more bipartisan direction since November. He joined a bipartisan group of senators pushing for a coronavirus aid deal and has stumped for money for states and localities — not exactly a popular position among conservatives. He also was among the first senators to meet with President Joe Biden at the White House.

He even gave an early hint that he might vote to advance Trump’s trial after voting to find the proceeding unconstitutional just a couple weeks ago. During a “Meet the Press” appearance on Sunday, Cassidy's colleagues noticed him arguing that the Senate's first vote on the constitutionality of Trump's trial included no debate time — while Tuesday's vote actually allowed the House Democratic managers and Trump’s lawyers to make their case.

That interview “kind of set the stage for being amenable,” said Sen. Mike Braun (R-Ind.). “You’ve got to take into consideration what your own point of view is as well as that of your constituents … he obviously was weighing those two.”

Of course, the blowback that Cassidy received is only a fraction of what might greet someone in a deep red state who votes to convict Trump. And he’s giving little away about how he sees the final verdict on a former president he voted to acquit in the first impeachment trial, just a year ago.

“I can’t begin to predict where he would be on the merits," said Sen. Mitt Romney (R-Utah).

Olivia Beavers contributed to this report.