Leo Varadkar has said the new National Maternity Hospital (NMH) will "absolutely" carry out clinical procedures contrary to the Catholic ethos.
Concerns have been raised about clinical independence at the new hospital after the Sisters of Charity transferred land ownership of the site to a new charity that will operate the hospital and lease it to the state.
Dr Peter Boylan, a former master at Holles Street, said that St Vincent's Holdings, the organisation to which the site is being transferred, "has a Catholic ethos" and that is "a fundamental problem".
He has also voiced his concern that procedures contrary to Catholic teachings such as abortions, IVF and sterilisations could be curtailed at the new hospital.
The Tánaiste denied this would be the case while speaking to On The Record with Gavan Reilly, echoing comments made by the Taoiseach that there will not be any religious influence on the new hospital.
"The decision of the Sisters of Charity to withdraw from healthcare, to give the land to a charity, is very significant," Mr Varadkar said.
"I want to respect the fact they have made that decision, some people have been giving them abuse at the moment and I think that's a little bit unfair when you look at the facts.
"We have an agreement that the hospital will be publicly owned and we have an agreement that any obstetric or gynaecological procedure that’s legal in the state, including terminations of pregnancy and IVF, will be legal in the new hospital, we’re comfortable around that.
"We have two difficulties, one is around the governance, the make-up of the board, we don't like that there are no representatives from the government on the board as it is currently proposed.
"And secondly, an issue around the land that the hospital will be built on because that's intended to be a long-term lease.
“I think I’m now hearing that either Vincent’s or the Sisters may be willing to sell that land, and if they are, we’re willing to buy.”
Mr Varadkar added that the issue of land ownership is being elevated to a higher extent by people than it needs to be.
"I would have a difficulty with the land we're leasing for the new hospital might be mortgaged," he said.
"The governance piece is important too because boards make decisions and we would like to have government reps on a board for obvious reasons and that's probably more important than the lease arrangement.
"But I will say this, and I think some people aren't acknowledging this, Holles Street, the National Maternity Hospital, is a Catholic-ethos hospital, at least on paper the chairman is the Archbishop of Dublin, although he wants to come off that.
"Notwithstanding that, Holles Street is a hospital in which terminations are performed, in which assisted reproduction is provided, so I think sometimes people can take this issue a little bit further than the facts will allow.
"I worked there, I did part of my training in the National Maternity Hospital, I never, ever felt that there was a nun or a priest looking over my shoulder when it came to giving the right care to women."
During the same interview, the Fine Gael leader also spoke about international travel and the target by his party to build 40,000 houses a year.