Senator Bill Cassidy was standing in line at a Home Depot in Baton Rouge, La., when a conversation with a woman in the store turned, as it often does in his home state, to his fraught relationship with the president.
“I say, ‘You know, I don’t really think President Trump likes me that much,’” Mr. Cassidy, a Louisiana Republican, recounted in a recent interview. “But we work really well together.”
That might be both an understatement and an overstatement.
Mr. Cassidy, who voted to convict Mr. Trump in his 2021 impeachment trial and who drew the ire of the “Make America Healthy Again” movement for his strong advocacy for vaccines, is now in the fight of his political life, largely because of the perception that he is insufficiently loyal to the president.
To many of his right-wing detractors, including the president, Mr. Cassidy committed the gravest possible sin when he was one of seven G.O.P. senators to vote to find Mr. Trump guilty of inciting an insurrection for the pro-Trump riot at the Capitol on Jan. 6.
That decision precipitated a major break between Mr. Cassidy, who spent six years in the House and has been a senator since 2015, and other Republicans in his state. It triggered years of animosity and insults from Mr. Trump, who labeled Mr. Cassidy a “total flake” and endorsed a Republican congresswoman, Julia Letlow, to unseat him.
On Saturday, voters in Louisiana will take the first step in deciding whether to carry out Mr. Trump’s wish, casting their ballots in a Republican primary that has been entirely defined by which candidate most closely adheres to the president’s ideology.
Mr. Cassidy’s fight for political survival has offered a vivid portrait of a Republican’s struggle to maintain some semblance of independence in a party that now prizes fealty to Mr. Trump above all else. A gastroenterologist who proudly led a vaccination campaign in Louisiana, Mr. Cassidy put his considerable reservations aside last year and backed the confirmation of Robert F. Kennedy Jr., a vaccine skeptic, as health secretary.
But the move has not earned him any good will from the president and has failed to ingratiate him with the MAHA movement, which has invested heavily in defeating Mr. Cassidy. His decision may have also alienated centrists who might have otherwise been inclined to back him.
“I haven’t met that many people who are enthused to go vote for him,” said Lionel Rainey III, a Republican strategist based in Louisiana. “He’s like a man with no country and a man with no party.”
The primary is widely expected to go to a runoff election next month. Under state law, if no candidate in the race gets above 50 percent of the votes, the top two will advance. Recent polls have been inconsistent, but they have suggested that no candidate is likely to win a majority of votes, and that Mr. Cassidy’s advancing is far from guaranteed.
Such an outcome would have once been unthinkable for an incumbent Republican senator who has a deeply conservative voting record, an influential perch in Washington, a significant fund-raising advantage and a history of delivering government funding to his state.
But Mr. Cassidy’s top two competitors — Ms. Letlow and John Fleming, the state treasurer — have drawn on the seed that Mr. Cassidy’s impeachment vote planted five years ago to argue that the senator cannot properly represent Republican interests in Washington.
“Louisiana is still not forgetting that, and they still hold it against him. And to be honest with you, he’s not helped himself,” Mr. Fleming said at a Republican event at a Baton Rouge cafe this week. “He’s never apologized for it. He never said he was wrong.”
Mr. Cassidy, who won his seat by relentlessly hammering a Democratic incumbent over her support for Obamacare, has bristled at the idea that one vote should define him politically.
“If somebody is fixated on events from five years ago, six years ago, they’re not thinking about the present and the future of our state,” he said on Thursday at an event in Lafayette, La. “This race is about the present and the future.”
The Louisiana Senate primary is one of several high-profile tests of how independent any Republican official can be in the Trump era.
The president and his political operation have similarly targeted Representative Thomas Massie, a Kentucky libertarian who is Mr. Trump’s most vocal Republican critic in the House, and has threatened state legislators who have bucked his demands on redistricting.
But whereas Mr. Massie seems to relish his position as a MAGA pariah, Mr. Cassidy, the chairman of the Senate’s Health Committee, has spent Mr. Trump’s second term burnishing his conservative credentials.
The senator has often pointed to his voting record in Congress, repeatedly highlighting that Mr. Trump has signed a series of bills he sponsored, or mega-bills that include provisions he championed.
His supporters believe that Mr. Cassidy has a proven history of delivering for his constituents. “I believe he’s a man of honor,” said Dr. William Schumacher, 72, of Lafayette.
But many of Mr. Cassidy’s critics have argued that his attempts to curry favor with Mr. Trump and his base were another kind of betrayal.
After agonizing over the move for weeks, Mr. Cassidy reluctantly backed Mr. Kennedy to take the helm at the Department of Health and Human Services.
That uneasy embrace did little to heal the rupture with the president, and it did not last. Mr. Kennedy recently blasted Mr. Cassidy after the secretary’s favored pick for surgeon general stalled, and his political allies in the “Make America Healthy Again” movement have thrown their support behind Ms. Letlow.
Mr. Cassidy’s vote for Mr. Kennedy may have cost him backing from the more moderate voters he needs to hang on to his seat. Rather than its usual open primary in which the top two contenders advance regardless of party affiliation, Louisiana has switched to a closed system in which Republicans and Democrats compete separately.
Mr. Cassidy’s campaign believes that unaffiliated votes are more likely to back him than Ms. Letlow or Mr. Fleming and have sought their support. Fifteen percent of ballots cast in the state’s early voting period came from what the state calls “no party” voters.
At the same time, Mr. Cassidy and his campaign have been working feverishly to convince Republican voters that he can best carry the state’s conservative mantle.
That effort was on display on Thursday in Lafayette, where Mr. Cassidy appeared with a prominent anti-abortion political group to highlight his record on that issue.
Mr. Cassidy and the top high-dollar political action committee supporting him have also spent $21 million on advertisements, according to AdImpact, an ad tracking firm. Many of those spots have attacked Ms. Letlow, a three-term congresswoman, as insufficiently conservative because of comments she made as she was interviewing to become the president of the University of Louisiana at Monroe in 2020.
At the time, Ms. Letlow, then a university official, praised diversity, equity and inclusion initiatives that have been excoriated by Mr. Trump. Ms. Letlow suggested that the school’s lack of diversity in its faculty was “shameful” and said she would aim to hire more diverse senior staff.
Those criticisms have sowed questions among conservative voters and may hinder Ms. Letlow’s push to win the state’s primary outright.
Over a dinner buffet with slices of pecan pie and cake at a meeting of Republican women in Lafayette on Wednesday, one attendee pressed Ms. Letlow on her stance on D.E.I.
Ms. Letlow, who has spent weeks polishing her response, said that DE.I. had been “hijacked by the left” and that she had “fought against it ever since.”
She has argued that she has reliably voted to advance conservative priorities since coming to Congress.
Louisiana voters “want someone who won’t turn their back on the voters that they represent,” she said in an interview. “They know that they can depend on me to do that.”
