Background: Healthcare workers (HCWs) are prioritised for COVID-19 vaccination. Analysing their vaccination preferences is crucial to understand suboptimal uptake and identify levers to increase acceptance among those hesitating.Methods: We administered an online single-profile discrete choice experiment among a snowballing sample of French HCWs, recruited December 2020 through January 2021. Respondents in three random blocks chose between accepting or rejecting COVID-19 vaccination across eight hypothetical scenarios. Vaccine eagerness was derived from decision certainty.Results: Among 4346 participants, 61·1% made uniform decisions, including 17·2% always refusing vaccination across all scenarios (serial non-demanders). Among 1691 respondents making variable decisions, a strong negative impact on acceptance was observed with 50% vaccine efficacy (compared to 90% efficacy: odds ratio 0·05, 95%-CI 0.04-0.06), and the mention of a positive benefit-risk balance (compared to absence of severe and frequent side effects: OR 0·40, 0·34-0·46. The highest positive impact was the prospect of safely meeting older people and contributing to epidemic control (compared to no indirect protection: OR 4·10, 3·49-4·82 and 2·87, 2·34-3·50, respectively. Predicted acceptance was 93·8% for optimized communication on mRNA vaccines and 16·0% for vector-based vaccines recommended to ≥55-year-old persons. Vaccine eagerness among serial non-demanders slightly but significantly increased with the prospect of safely meeting older people and epidemic control; and reduced with lower vaccine efficacy.Discussion: Vaccine promotion towards HCWs who hesitate or refuse vaccination, should avoid the notion of benefit-risk balance, while indirect protection effects with individual utility can lever acceptance. Vaccines with limited efficacy will unlikely achieve high uptake.Funding: This study was conducted with financial support from French Public Health Agency (SantéPublique France).Declaration of Interest: None to declare. Ethical Approval: The study protocol was approved by the IRB of CHU St Etienne (N° IRBN1092021/CHUSTE ) and the database was registered by EHESP French School of Public Health according to the GRDP regulation. Because the data collection was observational, collected no sensitive and only self-declared biomedical information, no informed consent was required. Participants visiting the study website saw the complete study information and agreed to study participation before starting the questionnaire. Study participation was anonymous without any risk of indirect identification.
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