The Tánaiste Leo Varadkar says there are issues with the booster system that need to be ironed out.
Over half of the 180,000 booster appointments made for last week were marked as 'Did Not Attend'.
It is believed some people are being offered multiple bookings for their booster - such as receiving it from their GP, but still being invited to attend a HSE clinic.
Mr Varadkar says the amount of 'no-shows' is unusual, suggesting a wider problem.
“Some vaccine centres that there's a DNA rate – a Did Not Attend rate – of as high as 50%.
"To me, that's unusual.
"In the health service, a 15% or a 20% DNA is not unusual - 50% is very high.
"I wonder if maybe there's problems in the booking system, or whether there's issues that need to be ironed out.
"I've heard, anecdotally, of people getting appointments when they've already had their third dose - or people getting two appointments or not being able to cancel them."
Earlier the chair of the Irish Medical Organisation's GP Committee, Dr Denis McCauley, said there are very few no-shows at general practice clinics.
He told Newstalk Breakfast: "I think it is a respect thing as well.
"People would be very loath to not turn up for a GP vaccine clinic because they know the GPs will know who they are the next time around.
"I think people need to realise that very soon the vaccines will take on a lot more promise, so now is the time for there to be no messing at all.
"If you get a vaccine appointment, make sure that you go there rather than getting your hair done or going shopping or if it is a work thing, stay on the helpline to get a new appointment.
"Be respectful of the mass vaccination centres - these are people who are working very hard, and it is very disrespectful to have over 80,000 people not turn up in one week. It is not appropriate."
Additional reporting: Kacey O'Riordan