Professor Gráinne Flannelly, the clinical director of the Cervical Check programme, has announced she is standing down from her role.
It follows the recent controversy over smear test results.
Prof Flannelly is said to have informed the HSE of her decision yesterday evening.
In a statement, she said: "I would like this evening to announce that I have taken a decision to stand aside from my role as Clinical Director of Cervical Check with immediate effect.
"I am sorry that recent events caused distress and worry to women. I have decided to step aside to allow the Programme to continue it’s important work."
She added: "I would like to take this opportunity to thank each and every one of the doctors, nurses and programme staff of Cervical Check for their continued hard work and commitment towards delivering a first-class service for the women of Ireland."
The HSE thanked Prof Flannelly for her "enormous dedication, contribution and expert knowledge" over 12 years.
Health Minister Simon Harris, meanwhile, has said the State will pay for repeat tests for any women who would like reassurance:
Have heard from many women today who have had smear tests & would like a repeat test to reassure them. Am arranging for this facility to be available & the State will meet the cost of the repeat test. Arrangements on how this will operate will be outlined next week
— Simon Harris TD (@SimonHarrisTD) April 28, 2018
The latest developments came less than two days after it was revealed that more than 200 reviews of tests suggested women with cervical cancer should have received 'earlier intervention'.
The latest Cervical Check figures were released after Vicky Phelan's case this week highlighted the issue.
Ms Phelan settled a case against a US lab on Wednesday, after being wrongly informed in 2011 that she had the all clear.
Three years later, a review found the results were incorrect.
She was diagnosed with cervical cancer around the same time, but she only found out about that review last year.
A full review into the cervical screening programme has been announced.
A helpline for any women with concerns was opened yesterday, and is available on 1800 45 45 55.
Minister Harris had said on Friday he currently cannot have confidence in the managers of the screening programme.