The new coronavirus vaccine will start being given to care home residents from Wednesday as part of a new pilot.
A designated care home in Betsi Cadwaladr University Health Board in north Wales will be the first in Wales to receive the Pfizer/BioNtech vaccination - which started being rolled out to frontline health and care staff and the over 80s on Tuesday, December 8.
The Welsh Government confirmed that teams in additional health boards will be taking the vaccine to care homes later this week.
There has been widespread concern about keeping the vaccine "stable" outside of hospital as it usually needs to be stored at -70C.
Discussions have been held between the Welsh Government and the Medicines and Healthcare products Regulatory Agency (MHRA) as well as the vaccine's manufacturer about how to re-package and transport the vaccine without compromising its safety and efficacy. This meant that until now it had proved a challenge to take the vaccine to care home residents.
However, it has been confirmed that health boards can take the vaccine to settings with at least five residents, rather than using it only in static vaccination centres.
Health Minister Vaughan Gething said: "Following Wales' successful roll-out of the first Covid vaccine last week, we are starting the care home resident phase of the programme carefully. However we need to continue to make sure we can safely transport the vaccine to people who can’t come to clinics.
"If all goes well this week, we will roll out care home vaccination ahead of Christmas, bringing a new level of protection to some of our most vulnerable people.
"Our NHS staff have done a fantastic job to get this first vaccine out in a safe and timely manner. I’m extremely grateful for their hard work on this and across the course of the pandemic."
Dr Gill Richardson, chair of Wales' Covid-19 Vaccine Programme, said: "The delivery of a Covid-19 vaccine to care home staff and residents has always been a priority for the Welsh Government.
"We have been working for months to meet the challenges of distribution and believe we have a feasible solution which we will deploy at pilot sites from Wednesday. Care home staff have been offered immunisation at health board centres whilst awaiting the mobile model to commence.
"We are now very confident NHS hospitals can safely repackage and transport vaccine to care home without compromising its stability."
The initial roll-out of the vaccine to care home staff, health and social care workers and those aged 80 and over began on December 8 across the UK based on advice from the Joint Committee on Vaccination and Immunisation (JCVI).
As further supplies become available and additional vaccines receive MHRA approval, the Welsh Government said a "staged approach" will see other groups being offered the vaccine based on risk of serious complications and deaths.
People are being urged to wait to be invited for the jab, which will happen through NHS systems, and not ask their pharmacist of GP.