He also said access to the UNESCO world heritage site, 12 kilometres off the south Kerry coast, would be allowed, in future, only when it was officially open to visitors and when official guides were on duty.
Mr Mansergh, who described the rock as “hazardous”, said difficult decisions needed to be made and the priority was to prevent further deaths.
Three overseas visitors have died in falls on the spectacular rock since 1995.
On Sunday, a 57-year-old American woman, Christine Danielson Spooner, from Rochester, New York, died after suffering serious head injuries in a 30ft fall.
The mother-of-two was with her husband, Richard, at the time.
On a visit to Kerry, yesterday, Mr Mansergh said her death would be a catalyst for a fundamental safety review.
“What happened is deeply regrettable, but Skellig Michael will never be entirely safe for anybody to visit. We have to be realistic about that,” he said.
There’s a stairway of about 600 stone steps, which do not have protective railings, leading to the 7th century monastic remains at the pinnacle of the rock.
The OPW has in the past ruled out railings and rope barriers for environmental reasons, saying it would detract from the integrity of the site.
But a spokesman confirmed a full investigation and review of all operationswould be carried out involving the health and safety of visitors and staff.
Mr Mansergh said he could understand the environmental argument and the aesthetic effects of altering the appearance of the rock, given that it was an ancient heritage site.
But, he also stressed the whole issue of safety would have to be looked at again, including possible protective measures at trouble spots, without prejudice.
Ms Spooner died in a fall from a ledge close to the spot where another American visitor, Joseph Gaughan, 77, from Wilkbar, Pennsylvania, lost his life, last May.
Mr Gaughan’s daughter, Rebecca Madden, yesterday said it was distressing to see another family having to go through the same trauma as her family.
Expressing a hope the rock would be made safer, she said she found it hard to believe another fatality could happen in so short a time.
About 14 boatmen take visitors to the rock from late May to late September, and a maximum of 11,000 visitors are allowed per year.
The season had not opened and there were no official guides on the rock on the day Mr Gaughan met his death. Normally, three to four guides live on the rock during the season.
Mr Mansergh said everybody would have to obey rules in relation to access. “Rules have to be abided by. Lives come before livelihoods,” he told reporters.
He had been due to meet Skellig boatmen yesterday, but the meeting was called off as a mark of respect to Ms Danielson Spooner.
Mr Mansergh said the review would cover staffing, public safety warnings and all interests, including boatmen and UNESCO, would be consulted.