Background <p>Health literacy is essential for understanding the coronavirus disease 2019 (COVID-19), dealing with health information, and making vaccine-related decisions. We aimed to determine the level of COVID-related health literacy, identify its determinants, and investigate the association between COVID-related health literacy and vaccine acceptance from a sample of adults in the Hungarian population.</p> Methods <p>In 2022, we surveyed 1200 Hungarian adults aged 18 and older. It was a probability sample of the Hungarian adult population. A polling company conducted computer-assisted personal interviews to collect data. The questionnaire included items on socio-demographics, health status, vaccine acceptance and COVID-related health literacy. The determinants of COVID-related health literacy and its association with vaccine acceptance were investigated by binary logistic regression.</p> Results <p>Almost half of the sample (43.6%) had a sufficient level of COVID-related health literacy. Being female (odds ratio, OR 1.46), having a tertiary education (OR 2.26), belonging to the normal social status in society (OR 1.74), average or (very) good subjective perception of family wealth (OR 2.08 and 3.28, respectively) and (very) good self-perceived health status (OR 2.58) were associated with a sufficient level of COVID-related health literacy. Vaccine acceptance was positively associated with a problematic or sufficient level of COVID-related health literacy (OR 2.55 and 2.57, respectively), older age (OR 1.02) and completing tertiary education (OR 1.98), while living in smaller cities (OR 0.52) or villages (OR 0.44) and being unemployed (OR 0.47) were negatively associated with vaccine acceptance.</p> Conclusions <p>Vaccine acceptance was positively associated with COVID-related health literacy and negatively associated with unemployment and living in a small town or a village. Therefore, we advocate for programs that targeting these groups to enhance vaccine acceptance.</p>