Last month it was announced problems with ventilation systems were among issues contributing to delays at two Aberdeen hospital buildings.
But a review shows "multiple concerns" about the issue were raised in 2020 and "do not appear to have been addressed".
NHS Grampian said it was addressing the points raised by the review.
The health board added that many of the issues raised by NHS Scotland were due to changes in guidance and processes in the wake of problems with new hospitals in Glasgow and Edinburgh.
The Baird Family Hospital and Anchor Centre were both meant to open in 2020 but a series of delays mean the overall project cost is now £261m - £98m more than the original estimate.
A review of the Anchor Centre project, which will provide services for haematology and oncology patients, was completed by NHS Scotland in March as part of work to ensure infection prevention and control are a key consideration in building new hospitals across the country.
The review found the project had three "significant" issues to address, including ventilation and drainage, and 15 more issues categorised as "major".
The report, released to BBC Scotland under freedom of information laws, shows that a previous NHS review produced in September, 2020 "identified multiple concerns in relation to the development of the ventilation strategy that, from the evidence presented, do not appear to have been addressed".
These concerns were raised a month after the Scottish Hospitals Inquiry was launched.
The input of NHS Grampian's Infection Prevention and Control (IPC) team is assessed by the NHS Scotland report.
The report also adds that "of significant concern" is a lack of assurance demonstrating stakeholder interaction and sign-off of developed strategies, particularly with respect to the IPC concerns.
Concerns about contractors' lack of experience on healthcare building projects was also raised, as were a number of governance issues.
The Anchor centre is expected to open in October and the Baird Family Hospital, which will provide maternity and breast screening services, as well as a neonatal unit and operating theatre, is meant to open in September next year.
The buildings will be located next to Aberdeen Royal Infirmary.
The Covid pandemic, a work fatality on site and a contractor going into liquidation have all also added to the project's overall delays.
An NHS Grampian spokesman said the board "welcomed the robust scrutiny" in the NHS Scotland report and said it was "actively working" with them to improve the areas highlighted.
He added: "Many of the points raised are due to changes in guidance and process, that came following issues with the Queen Elizabeth University Hospital in Glasgow and the Royal Hospital for Children and Young People in Edinburgh.
"In the majority of cases, our teams were already aware of and actively working to address the issues and opportunities raised.
"Our IPC team is now embedded within the project board delivering these complex clinical buildings, so that when the Anchor Centre and Baird Family Hospital open their doors, they will provide the best possible levels of care for patients. "