Nursing and other healthcare students who refuse to be vaccinated against Covid-19 are now banned from taking up clinical placement in HSE facilities.
The HSE decision could see some students fail the clinical placement module of their course or require them to repeat a year.
The new rule relates to unpaid clinical placements and does not apply to fourth-year nurses considered part of the HSE workforce.
In a letter to third-level institutions, the HSE's chief clinical officer, Dr Colm Henry, said the new measures are necessary for "the safety of patients, staff, and students".
"We are all agreed that the safety of patients, staff, and students remains a shared key priority.
"Following consideration, the HSE Covid-19 Vaccination Working Group has taken the following decision, and I ask that your institutes now apply this to all student placements in HSE facilities with effect from April 1, 2021.
"Students that are eligible for vaccination, that has been offered vaccination and decline vaccination should not be assigned to clinical placements in HSE facilities.
"This may be reviewed as the epidemiological situation evolves."
The HSE says the rules apply to all students except in "very exceptional circumstances where there is specific and documented medical contraindication to vaccination for a healthcare student."
One second-year student nurse told the Irish Independent she does not wish to be vaccinated with the mRNA vaccines – Moderna or Pfizer - but would consider another Covid-19 vaccine.
The Galway woman’s position on mandatory vaccination for students has cast her in the minority among her classmates.
"Almost all of my classmates have taken the vaccine already, but when I discussed it with them, I heard many say we should all have a choice. Nobody should be forced.
"I am not against the vaccine, and I am happy for anyone who wants it and has received it.
"And I'm sure it is a very good vaccine for a lot of vulnerable people.
"We have the right to body autonomy. Nobody can force anyone to take any medication they don't want to take.
"We are taught about informed consent all through college.
"I think they would need to change the law before they could force people to leave their course after two years of studying.
"I am not anti-vaccine. My children are all vaccinated."
Prof Pete Lunn of the ESRI behavioural research unit said he and his colleagues have carried out an extensive study on vaccine hesitancy which will be published shortly.
He said they have found a slow and steady increase in acceptance in the vaccine with people saying they are definitely going to take it.
In the study, Dr Lunn said, "one of the fascinating things that showed up is that it wasn't so much scare stories or worries about side-effects that were the primary things driving vaccine hesitancy.
"The people who were the most hesitant were actually not understanding or knowing the benefits.
"We did some explicit tests on people's knowledge, and we found those who are hesitant were the least likely to be following Covid news and the least likely to have read about the vaccines.
"And therefore, were the least likely to know how effective they are.
"I think that tells you something important, in that there is still an awful lot of the message to get out about how effective these vaccines are to a significant minority of the population.
"What is partly driving the increasing numbers of people saying 'Yes, I will take it,' is people becoming more aware of how effective these vaccines are."
Deputy chief medical officer Ronan Glynn said there was "absolutely no complacency at policy level about vaccine hesitancy or confidence.
"I have been talking about it since last December; I am very concerned about the issue of vaccine hesitancy.
"It will be one of our major challenges to ensure people's legitimate concerns are answered.
"We know, looking at the issue of vaccine hesitancy over the last number of years, it will be the GP, it will be the community pharmacist, it will be health care professionals living and working in their communities who sit down with people who have concerns - it is those conversations that will ultimately convince the majority of people to take the vaccine," he said.