Health minister Vaughan Gething will face a vote of no confidence today.
It comes in the wake of the report published into maternity services in Cwm Taf.
A motion has been put forward by Plaid Cymru which will be debated in the Senedd after 4pm.
The party's health spokeswoman Helen Mary Jones said that the decision to put the motion forward came after last week's report on Cwm Taf, as well as others, including a 2014 the Andrews report on the Princess of Wales Hospital and Neath Port Talbot Hospital and about the Tawel Fan ward at Ysbyty Glan Clwyd published in 2015 and 2018.
She said she did not make the call for him to resign lightly, but that the responsibility for health lies with the minister.
On Tuesday, First Minister Mark Drakeford was asked in the Senedd siambr if he had confidence in Mr Gething - who stood against Mr Drakeford in the Welsh Labour leadership contest.
Conservatives leader Paul Davies asked Mr Drakeford "given this catalogue of failures, why haven't you sacked your health Minister?"
Cwm Taf maternity scandal: Health board boss admits chances to spot the problems were missed
Mr Drakeford responded: "I think that last remark simply trivialises the importance of the issues that the Member rightly pointed to earlier in his question.
"It is the serious actions that the Minister has taken, and those actions will go on, because he's to be advised on any further action required to improve maternity services in Cwm Taf, as a result of the arrangements that he has put in place.
"That's a serious reaction to a genuinely serious position, and that's the sort of health service and that's the sort of Government that I think people in Wales are entitled to see and to continue to see in the future."
Ms Jones said: "Calling for the resignation of a minister is not something that should be done lightly, however, last week’s report on maternity services in Cwm Taf was one of the most shocking and distressing reports of any organisation under the control of the Welsh Government.
Cwm Taf maternity scandal: Mum's baby died after she gave birth in the toilet of a labour ward
"Children died. Families have been traumatised. I cannot stress the seriousness and the extent of these failings. What more has to happen before the Minister takes responsibility? Ministers have resigned for less in the past.
"What happened at Cwm Taf is part of a wider pattern of system failures in quality of care and governance of health boards in Wales with three major scandals in the last six years, from poor patient care in Bridgend at ABMU to Betsi Cadwaladr and mistreatment of patients at Tawel Fan.
Vaughan Gething speaking about the Cwm Taf scandal:
"Responsibility for the health service lies with the Health Minister.
"The minister is the one who appoints the health boards, and the minister is responsible for issuing guidance to the health boards and setting how they operate. Time and again, the Health Minister has not only failed to get to grips with the challenges facing our Welsh NHS but has failed to take responsibility for such failings as well.
“There have been no resignations following the Cwm Taf scandal. The families deserve justice. I ask again, what more must happen before this is taken seriously?
“Today it will be for all Assembly Members to decide if they have confidence in our Health Minister. But whatever the outcome of this motion I have promised Cwm Taf families that I will never forget what they went through.
"We will do all we can to hold Government and the health board to account to try to ensure that the needed change is delivered."
