Objectives: A legally regulated program of mandatory vaccinations is in place in Poland. The number of vaccination refusals increased from 3437 to 48 609 in 2010–2019. The aim of the study was to determine the association of various socio-demographic factors with the attitudes of the residents of Poland to prophylactic vaccination. Material and Methods: The study was based on a secondary statistical analysis of a representative sample of 977 adult residents of Poland (a cross-sectional questionnaire-based study). Data was purchased from the Public Opinion Research Center. Results: The study group was characterized by a high level of acceptance of vaccinations. At the same time, nearly a third (31%) of the subjects agreed with the statement that vaccination is promoted mainly because this is in the interests of pharmaceutical companies, and more than a fifth (22%) of the respondents believed that vaccines for children can cause serious developmental disorders, including autism. A detailed multivariate analysis based on logistic regression revealed that being deeply religious (compared to being a non-believer) and living in a town with a population of 20 000–499 999 (compared to living in a rural area) were strongly associated with a very high acceptance of the anti-vaccination content. The opposite attitude was associated with having an average or good financial situation (compared to a poor financial situation), having completed vocational education (compared to primary education) and being ≥65 years old (as opposed to being <30 years old). Conclusions: Most socio-economic factors analyzed did not influence the respondents’ attitudes to prophylactic vaccination or showed little influence. Strong anti-vaccination beliefs were associated with being deeply religious and living in a town with a medium-size or small population. Int J Occup Med Environ Health. 2021;34(1):121–32