The chair of the National Paediatric Hospital Development Board has stepped down from his position.
Tom Costello has said it is due to concerns about "reputational damage" that the ongoing commentary about the increased cost of the national children's hospital is causing.
The board is responsible for overseeing the building of the new hospital.
It comes after it was revealed that a review of the rising costs of the hospital was told to stop short of finding individual culpability.
The Oireachtas Public Accounts Committee has heard the total cost of the project will be around €1.7bn.
The estimated cost for the hospital - which will be located on the campus of St James's Hospital in Dublin - has risen from an original estimate of €650m.
In a statement, Mr Costello said: "I have had the honour and privilege of Chairing the National Paediatric Hospital Development Board since my appointment by former Minister for Health, James Reilly in 2013.
"Since I assumed that role I have worked with the sole objective of ensuring that children and families in Ireland finally get the new children's hospital that they badly need and deserve.
An artist's impression of the new national children's hospital | File photo
"Since the board was appointed almost six years ago the hospital project has achieved many significant milestones.
"We are now at the point where the building is well underway and the New Children's Hospital will be completed in 2022.
"I have acted with professionalism and integrity in all my dealings with the project stakeholders including the Minister for Health and his department.
"Every decision made by the board has been guided by what was deemed best for the project."
But he added: "I am concerned about the reputational damage that the ongoing commentary about the increased cost of the hospital is having on this critically important project and so I have decided to step down from my role to help ensure that focus is restored on delivering the project."
He also paid tribute to the members of the board.
Health Minister Simon Harris has accepted his resignation.
In a statement, Mr Harris thanked Mr Costello for his service and "exceptional commitment" to the project.
"Throughout his tenure, Mr Costello worked tirelessly to ensure a state-of-the art facility is built for our children and advanced the project significantly", Mr Harris added.