Aims: The novelty of the COVID-19 pandemic and fast-developed vaccines may increase concerns about the safety and effectiveness of the COVID-19 vaccine and thereby influence vaccine hesitancy. The aims of this study were to examine (a) the main reasons for COVID-19 vaccine hesitancy and (b) factors associated with COVID-19 vaccine hesitancy. Methods: A nationwide survey was conducted in the autumn of 2021 when most Danes had received at least one dose of a COVID-19 vaccine. The sample ( N=13,570) was based on a random selection of individuals (⩾15 years), and data were collected via self-administered mailed questionnaires (digital and physical). The participants were asked whether they had been vaccinated against COVID-19, and if they had not, they were asked about their reasons for vaccine hesitancy. Logistic regression models were used to determine factors associated with vaccine hesitancy. Results: In all, 5,384 (39.7%) individuals completed the questionnaire. The main reasons for vaccine hesitancy were worries about adverse effects (57.6%) and the belief that natural immunity is better than vaccination (43.8%). Factors associated with vaccine hesitancy included female sex, younger age, being divorced, a country of origin other than Denmark, lower educational level, being unemployed, previously infected with COVID-19 and being worried to a greater extent about oneself and others getting infected. Mental health indicators were not associated with vaccine hesitancy. Conclusions: COVID-19 vaccine hesitancy is likely to pose a challenge for population immunity. To reduce vaccine hesitancy and increase vaccination uptake, future vaccination programmes should focus on specific socio-demographic subgroups identified in this study.