The Republican senator Bill Cassidy lost his primary on Saturday, as voters in Louisiana opted instead to advance two challengers to a runoff election after an extraordinary intervention by Donald Trump to oust the incumbent.

Cassidy’s bid to win the Republican party’s nomination for a third term in the deep-red state was imperiled by his decision to vote in favor of Trump’s conviction after the January 6 insurrection. In what was widely seen as an effort to rehabilitate his standing with the president, Cassidy last year cast the deciding vote to advance vaccine skeptic Robert F Kennedy Jr’s nomination to lead the Department of Health and Human Services, flying in the face of the senator’s support for immunizations and training as a physician.

Earlier this year, Trump encouraged the US representative Julia Letlow to enter the Senate race, and offered his endorsement in a bid to unseat Cassidy that now has paid off. Trump lambasted Cassidy on Saturday morning, calling him “a disloyal disaster” and “a terrible guy” on social media. Trump criticized the senator’s impeachment vote and said “he’s going to get CLOBBERED”, adding that Letlow was “a winner who will NEVER let you down”.

With 98% of the vote counted, the Associated Press reported that Letlow received 45.2% of the vote in the primary, against John Fleming, the state treasurer and former US representative, who received 28.3%. Cassidy came third with 24.4%. The race now heads to a runoff scheduled for 27 June.

Cassidy’s defeat underscores the perils Republicans run when they break with Trump on major issues. Earlier this month, five of the seven Republican Indiana state senators who halted a Trump-backed effort to gerrymander the state in Republicans’ favor lost their primaries. In North Carolina, Republicans are in a high-stakes battle to keep hold of one of their US Senate seats because Thom Tillis has opted to retire, after breaking with Trump last year over his top domestic policy bill.

Louisiana’s Republican party censured Cassidy following his vote to convict Trump, an ultimately unsuccessful effort in which he was joined by six other Republican senators, most of whom have now left office. Cassidy later supported a fruitless attempt to establish an independent commission investigating the insurrection, and called on Trump to end his 2024 re-election bid after his indictment for allegedly possessing classified material.

Even after voting to advance Kennedy out of the Senate health committee, which he chairs, and then for his confirmation, Cassidy has criticized some of his policies as secretary. He also opposed Trump’s attempt to have wellness influencer Casey Means confirmed as US surgeon general, leading Trump to blame the senator for having to withdraw her nomination.

Changes to Louisiana’s primary system likely worsened the prospects for Cassidy’s political survival. In 2024, Republican governor Jeff Landry, a prominent Trump supporter, worked with the legislature to change the rules of the state’s US Senate primaries so that candidates are nominated only by party members and unaffiliated voters.