Introduction Little is known about the impact of mandatory vaccination on people who are reluctant to be vaccinated, despite the potential importance in terms of public health policy. Objective We aimed to explore the relationship between vaccine hesitancy and onset, severity and characteristics of self-reported adverse events. Methods We used a cross-sectional online survey conducted in 2021 among a representative sample of the French population aged 18 years and older (n = 1593). All reported adverse events were analyzed and categorized by trained experts in drug safety and pharmacovigilance. Multivariate binomial regressions on the onset of self-reported adverse events, vaccine hesitancy categories and predefined responders’ characteristics were performed. Results Overall, 590 (37.0%) participants reported at least one adverse event, with 121 (20.5%) considered it to be severe. Proportions of reported adverse events, ranging from 18% (in non-reluctant responders) to 65% (in very reluctant responders), and their severity, ranging from 5% (non-reluctant responders) to 41% (very reluctant responders), depended highly on attitudes toward vaccination. The adverse events profile remained similar between groups. In the multivariate regression model, beyond attitude toward vaccination, younger age and female gender were significantly associated with higher reporting of vaccine adverse events. Conclusions Our results suggest that vaccine hesitancy could be a major driver of patient-reported vaccine-related adverse events and their perceived severity. In this context, vaccinators must pay special attention to reluctant patients and inform them on the possible nocebo nature of these adverse events so as to prevent them.