Neill-Fraser had her second appeal against her 2010 conviction quashed by a panel of three judges on Tuesday.

Justices Helen Wood and Robert Pearce rejected Neill-Fraser's appeal while Justice Stephen Estcourt made a dissenting judgement with an order for a retrial.

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Justice Wood said she had reached the conclusion that the evidence relied upon for the appeal was neither fresh or compelling and that there had not been a substantial miscarriage of justice.

Neill-Fraser was sentenced to 23 years in jail for killing her defacto partner Bob Chappell onboard their yacht Four Winds on Australia Day in 2009.

Mr Chappell's body has never been found.

She first appealed her conviction in 2012, but that was dismissed.

The Tasmanian Parliament in 2015 passed legislation which would allow for subsequent appeals against a conviction if they relied on fresh and compelling evidence that was not examined in an original trial.

It was this legislation that allowed her legal team to examine evidence concerning DNA from a then homeless teenage girl that had been found onboard the Four Winds.

At the appeal hearing this year, Ms Vass told the court she was onboard the yacht with two men the night Mr Chappell disappeared and Neill-Fraser was not.

She said one of the men had attacked Mr Chappell.

Ms Vass recanted that evidence a day later.

Her evidence was then abandoned by Neill-Fraser's legal team.

Outside court, Neill-Fraser's supporters said they would focus on obtaining justice outside the legal system by pushing for a Commission of Inquiry into the matter.

Neill-Fraser's daughter Sarah Bowles said the family was limited by the appeals process.

"Mum is now facing 13 Christmases in prison," she said.

"She hasn't spent a single Christmas with my kids and that's obviously very devastating.

"There's nothing that's going to undo the institutionalising effects this has had on mum both physically and psychologically."

Neill-Fraser supporter Rosie-Crumpton Cook said it was not the role of the Director of Public Prosecution to defend conviction, rather to ensure justice had been served.

"Susan Neill-Fraser has been denied justice," she said.

Ms Crumpton-Cook said a Commission of Inquiry would give people certain protections to speak out about the disappearance of Mr Chappell.

"There are prominent people in Tasmania that know Sue is innocent, but have chosen to remain silent while the matter was before the court.

"It is now time for those people to speak out."

Former premier Lara Giddings said there had been concerns about how the case was handled from day one.

"This matter will not go away, it cannot go away, we cannot afford for it to go away otherwise we will have other innocent people locked up in our prisons because of the failure to investigate on day one," she said.

Ms Giddings said Ms Vass should have been better supported during the proceedings and that the names of the men mentioned in her testimony should have been suppressed

"As soon as those names were published, her life was in danger," Ms Giddings said.

"She was not supported as a vulnerable witness, a key witness who could have proved the innocence of Sue-Neill Fraser.

"We cannot today say that what we've seen is justice from the Tasmanian courts."

Neill-Fraser will be eligible for parole next year.

Ms Bowles said she believed her mother would continue to fight her name.

She acknowledged in any application for parole, responses to a conviction such as appeals and protestations of innocence would be considered. "After a person has spent this long in prison, there is a lot of fear often coming out in the community about how they'll be received," Ms Bowles said.

"This case has obviously attracted a lot of positive attention, but there is also a lot of vitriol and hate directed towards us as a family.

"It's really a tragedy and it is one we need to focus on and resolve and I'm going to do everything in my power and I know that we have got a huge number of people who are going to continue to fight for this to see justice achieved."

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