The murder of Deborah Meindl was savage and sudden: Ms. Meindl, a nursing student with two young daughters and an unfaithful husband, returned to her small home just north of Buffalo, N.Y., and was stabbed, beaten, and strangled with a necktie, her hands cuffed behind her back.

More than 32 years after that February afternoon in Tonawanda, opening arguments are expected Friday in the trial of a man accused in her slaying — for the second time — as the Erie County district attorney, Michael J. Keane, tries to secure a conviction despite a lack of physical evidence and potentially exculpatory DNA.

The case’s history includes dead witnesses, overturned convictions and wild accusations from a famed criminal. And, overshadowing it all, the lingering question of why justice has been so hard to find, both in the 1993 killing and, in the minds of the defense, for the two men accused of it.

A year after the attack, Brian Scott Lorenz, known as a petty thief, was convicted of the murder largely on the testimony of a collection of unsavory associates and a single collectible coin, linked to the Meindl family, that was found in a car that Mr. Lorenz had stolen. James Pugh, a casual friend of Mr. Lorenz, was also convicted of the murder, which prosecutors posited had stemmed from a burglary gone wrong.

In 1994, both men received life sentences, despite steadfastly declaring their innocence.

But in August 2023, Justice Paul B. Wojtaszek of State Supreme Court set aside the convictions of both men, noting that genetic material taken from the crime scene did not match either defendant and that prosecutors had not revealed certain evidence to the defense.

The judge, in Erie County, N.Y., home to Buffalo and Tonawanda, granted new trials to both Mr. Pugh, who had already been released on parole, and Mr. Lorenz, who has remained in custody and has been denied bail.

Despite a paucity of physical evidence and the fact that many of the original prosecution witnesses are dead, Mr. Keane has decided to retry both men. Mr. Lorenz’s case began with jury selection on Monday in Buffalo, while Mr. Pugh’s is scheduled for December.

Defense lawyers for both men have wondered aloud why their clients are still being accused of a crime despite the DNA findings and the flaws cited by Judge Wojtaszek in the prosecution’s initial case.

“The death of Deborah Meindl was a terrible and tragic event, but Scott Lorenz is 100 percent innocent of this crime,” Mr. Lorenz’s lawyer, Ilann M. Maazel, said. “He had absolutely nothing to do with this.”

Zachary Margulis-Ohnuma, a lawyer for Mr. Pugh, seconded that: “Scott Lorenz is just as innocent as he was when he and Jimmy Pugh were framed in 1994.”

Mr. Keane’s office declined to comment on the case. The new trial for Mr. Lorenz is expected to take several weeks.

Though the exact shape of the prosecution’s case is unclear, the district attorney’s office will most likely need to rely on the words of witnesses who testified in 1994, but have since died.

In such unusual situations, prosecutors are allowed to read the old testimony to the jury.

“It poses a problem for everybody, including the jury,” said Hermann Walz, a criminal defense lawyer and an adjunct professor at John Jay College of Criminal Justice.

Jurors often determine the credibility of witnesses using behavioral clues: “Did they say it fast, did they say it slow, did they hesitate?” Mr. Walz said. “Looking at a witness is the whole reason we have the right to confront a witness.”

The Meindl murder has drawn intense interest as a result of efforts to exonerate Mr. Lorenz and Mr. Pugh, and several explosive allegations that have emerged as the case was examined anew.

In 2018, lawyers for the men persuaded a state judge to order new DNA testing on crime-scene evidence. The results were stunning: Neither Mr. Pugh’s nor Mr. Lorenz’s DNA was present. The new testing did find evidence, however, of an unknown individual on a variety of items, including a knife used in the attack, Ms. Meindl’s bloodied clothes and the necktie she was strangled with.

With pressure building, John J. Flynn, then the county district attorney, ordered a new investigation in 2021, giving the job to two veteran prosecutors.

But rather than finding new evidence of the convicted men's guilt, the prosecutors came to an eyebrow-raising conclusion: that the real killer was Richard Matt, a convicted killer from the Buffalo area who was also a close friend of a local detective, David Bentley, who had helped lead the investigation into Ms. Meindl’s murder.

Mr. Matt later became infamous as one of two men — along with David Sweat — who escaped from a maximum-security state prison in Dannemora in 2015. He was fatally shot at the end of a three-week manhunt.

Mr. Sweat was recaptured alive, and later suggested to the prosecutors reinvestigating the Meindl murder that Mr. Matt had told him he was involved, an allegation he repeated during a multiday hearing on the case in late 2021 and early 2022.

But Judge Wojtaszek, in his 2023 decision, said he found Mr. Sweat’s account “patently incredible” and also cast doubt on the prosecutors’ findings, calling them “nothing more than speculation, conjecture and surmise without any substantiation or corroboration.”

In addition to some witnesses, several other characters in the Meindl case have also died, including Donald Meindl, the victim’s husband, who was initially considered as a possible suspect. Mr. Meindl, who died in 2023, had been having sex with an underage girl he worked with at a Taco Bell at the time of the murder and had talked to an associate about having his wife killed, according to transcripts of the 1994 trial. (He later said those comments were a joke.)

But Mr. Bentley, working for the Tonawanda Police Department, used a confidential informant to develop an alternate theory implicating Mr. Lorenz, who had been engaged in minor thefts in Buffalo. Mr. Lorenz was in his early 20s at the time and was being held in Iowa on an auto theft charge; he later said he initially confessed to the murder, and implicated Mr. Pugh, in order to get out of that jail. He assumed the truth would soon come out and exonerate both of them.

That did not happen. Now Mr. Lorenz, 56, will once again sit in a Buffalo courtroom, waiting for a jury to decide his fate.

In a 2024 interview, he said he was worried he might never be released, despite his conviction being tossed.

“It just seems like it’s never going to end,” he said. “I’m on a treadmill, in a tunnel, with the light at the end. But it’s just not getting nowhere, man.”