HSE Chief Executive Paul Reid has announced that he will be stepping down from his position later this year.
Mr Reid, whose pay package topped over €400,000 last year, will step down in December, saying he has no immediate career plans.
In a message to staff today, Mr Reid said that he was making the decision with a heavy heart, and that it was the hardest decision he had ever made in relation to his career.
Mr Reid said his decision was influenced by a desire to spend more time with his family, and a "belief that the HSE was entering a new phase and that the appointment of a new leader was now timely".
His departure comes after that of former HSE Chief Operations Officer Anne O'Connor, as well as Chief Medical Officer Dr Tony Holohan, and Deputy Chief Medical Officer Dr Ronan Glynn.
"Working in the HSE has been by far the greatest period in my career," said Mr Reid.
"It has been truly rewarding leading an organisation whose staff come to work every day to make people's lives better."
"No organisation will ever match the commitment, dedication and relentless willingness to go beyond the call of duty that I have witnessed," he added.
Paying tribute to Mr Reid, HSE Chairman Ciarán Devane said Mr Reid led the health service through "the greatest challenge it has ever faced", doing so "with relentless dedication and professionalism".
"We are very grateful that he will stay in his role for a further period to allow us progress the extremely difficult task of replacing him."
Taoiseach Micheál Martin paid tribute to Mr Reid for his leadership during the Covid-19 pandemic, saying he had "led from the front" with his team.
Mr Martin said people are entitled to make personal decisions in respect of their lives and careers.
He said he had a good relationship with Mr Reid, who was available 24/7 during the pandemic.
He also said there was "no connection" between Paul Reid's comments on radio yesterday about Our Lady's Hospital Navan and his resignation today.
In a statement, Minister for Health Stephen Donnelly said Mr Reid led Ireland's health service through some of its most difficult days, with dedication and professionalism.
"Since his appointment as Chief Executive in June 2019, Paul Reid has provided exemplary leadership to the HSE," he commented.
"Throughout the pandemic, Paul played a critical role in leading Ireland’s response to the greatest health emergency of our times.
"He leaves behind him an organisation much enhanced for his time as Chief Executive and one that is already making real progress in implementing reform and improvement across many aspects of healthcare provision.
Mr Donnelly added: "I want to wish Paul all the best for the time ahead and to thank him and his family for the many sacrifices they have made over the last three years to allow him to dedicate himself to the role of CEO."
Sinn Féin's Health Spokesperson David Cullinane wished Mr Reid well, saying it was a "big decision" for him personally.
"As we look forward, our health services need strong, decisive leadership primarily from the Minister for Health supported by the Department and HSE," Mr Cullinane said.
Co-leader of the Social Democrats Róisín Shortall said it is a "matter of concern" that another senior person within the health service is leaving.
Speaking on RTÉ's Drivetime, Deputy Shortall said the "exodus from the top" will lead to a "huge loss of experience and expertise".