Larry Fisher died on Tuesday while serving a life sentence for rape and murder at the Pacific Institution in Abbotsford, B.C., said Correctional Service Canada. He was 65.
"It's not an unexpected death," said Samantha Cater, a prison spokeswoman. "There's nothing suggesting any foul play."
Milgaard was a teenager when he was wrongfully convicted of killing Saskatoon nursing aide Gail Miller and he spent 23 years in prison trying to prove his innocence.
He was travelling with friends through the Saskatchewan city at the time of the killing.
The Supreme Court of Canada eventually quashed Milgaard's conviction in 1992, with the emergence of new DNA evidence linking Fisher with the murder.
Fisher was convicted of the crime eight years later and sentenced to life.
When contacted, Milgaard's sister, Susan Milgaard, said the family had discussed the matter and decided not to comment.
Milgaard's lawyer Hersh Wolch said in an interview that he had cross-examined Fisher on two occasions.
"My impression was that he was pure evil," said Wolch. "I mean, the horrific things he did to people, and topping that off with letting David languish in jail for all those years put him on the upper level of evil people.
"One doesn't like to speak ill of the dead, (but) it's certainly impossible to speak good."
Wolch said the Milgaard case became a symbol for what can go wrong when police have "tunnel vision" and showed that a conviction doesn't necessarily mean someone is guilty.
Defence lawyer Gary Botting who wrote a book about wrongful convictions in Canada said police leaped to the wrong conclusions in the case.
"It's all about coincidence and serendipity," he said.
He said Fisher had the opportunity but chose not to come forward and exonerate Milgaard.
"That's almost the saddest commentary of all, that he would allow an innocent man to spend 23 years in (prison)," said Botting.
An inquest launched by the Saskatchewan government in the wake of the case led to a multimillion-dollar compensation package for Milgaard, as well as a raft of reforms to prosecution and policing in Canada.
"It was huge," said Botting. "People just didn't believe that kind of injustice could be done."
Changes included a new code of ethics for Crown lawyers and police forces, and evidence from jailhouse "snitches" would no longer be considered reliable.
"It's just shocking to think that Canada would have allowed this to happen," said Botting. "You're taken out of circulation for 23 years. It's going to affect you forever, for the rest of your life."
— By Geordon Omand in Vancouver
— Follow @gwomand on Twitter