Nicola Sturgeon has been told "heads should roll" after the opening of the Royal Hospital for Children and Young People in Edinburgh was delayed for at least another year.
At First Minister's Questions, the Scottish Tories' acting leader Jackson Carlaw criticised the Scottish Government over the "absolute shambles" surrounding the new hospital.
Carlaw accused Health Secretary of doing "too little, too late" in addressing the problems after she announced on Wednesday the site would until at least next autumn.
The hospital was originally scheduled to open by the end of 2012.
Claiming more than 300,000 children have missed out on emergency care at the new site due to the long-running delays, Carlaw said: "Four health secretaries, blunders, cost overruns and yet it's only yesterday that the Scottish Government decides to appoint a troubleshooter to sort this mess out.
"The Sick Kids' Hospital is just 10 minutes' drive from where we all are now and yet it seems that four successive health ministers chose either not to know or simply failed to ask about the full extent of the problems faced until way, way too late."
He added: "This is a saga from which nobody emerges well. Not the health board, not the contractor and certainly not this Government - and it's altogether sadly too predictable.
"I think the country thinks - for once - heads should roll."
The First Minister acknowledged the situation was "unacceptable".
She said: "To say that the Health Secretary and I are angry at this situation would be an understatement and I know that anger is shared by patients and staff."
Sturgeon pledged "closer scrutiny and oversight" on the project.
She said: "The focus of the Scottish Government is on putting this right.
"We will not allow the hospital to open until we are satisfied about patient safety."
Sturgeon referenced the two reports released on Wednesday, which found the ventilation issue that has caused the latest delay did not come to light until the start of July.
"I didn't know about that, the senior management in the health board - as far as I'm aware - didn't know about that and the Health Secretary didn't know about that," she said.
"As soon as that came to light, the Health Secretary acted properly and appropriately.
"It would have been wrong to allow that hospital to open before assurances about patient safety could have been given."
She added: "There has been substantial work done over the summer to make sure any other issues have been identified.
"I deeply regret that the hospital will be opening late - extremely late - and it is important that we make sure that every issue that has been identified is addressed so that when it does open it is safe for the patients who use that hospital."
The Health Secretary revealed the extra work to make the hospital safe was estimated to cost an additional £16million, in addition to having cost £16million on monthly payments for the vacant site as well as the cost of continuing to run the existing hospital site.
Scottish Labour leader Richard Leonard also asked about the hospital and reiterated his party's calls for a public inquiry.
He said: "Does the First Minister not understand just how angry people are about this?
"We've got a children's hospital in Edinburgh that can't open its doors and we were reminded at the weekend that we have a hospital in Glasgow built by the same contractor that has been closing its doors to a children's cancer ward, and Audit Scotland is saying that there needs to be a review of whole project contracting to help with preventative and reactive measures.
"We need to get to the bottom of this. We need full public transparency to restore public trust so what will it take for the First Minister to finally listen and deliver a full public inquiry into this abject failure of governance and government?"
