Introduction. The introduction of antiCOVID-19 vaccination has brought a variety of challenges in the vaccination campaign. The aim was to identify challenges at the primary health care (PHC) institutions with respect to the national anti-COVID-19 vaccination campaign in the Republic of Moldova. Material and methods. The study was included 61 medical worker respondents from 39 PHC vaccination centers, between October and November 2021. The list of evaluated centers was proposed by the Ministry of Health. The activities were carried out using the World Health Organization supportive supervision tool. Results. The analysis of the interview results identified that the medical staff reported being overworked, physically and morally exhausted. Only 2/3 of the interviewed staff felt safe in performing immunization procedures, a substantial part being unsure of the effectiveness of personal protection measures at the workplace. The most common challenges in the management of anti-COVID-19 immunizations were the refusal of the population to be vaccinated due to a lack of trust in the vaccine, caused by the negative influence of social networks, cult servants, myths and fake news, insufficient involvement of public administration in promoting vaccination and lack of vaccines preferred by the population. Conclusions. Immunization against COVID-19 has caused challenges for PHC. Overworked staff, insufficiently informed population, myths, as well as the lack of vaccines requested by patients, generated the greatest challenges in achieving vaccination.