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Background: This study investigated the determinants of coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare workers (HCWs) in Cameroon and Nigeria., Methods: This analytic cross-sectional study was conducted from May to June 2021, including consenting HCWs aged ≥18 y identified using snowball sampling. Vaccine hesitancy was defined as indecisiveness or unwillingness to receive the COVID-19 vaccine. Multilevel logistic regression yielded adjusted ORs (aORs) for vaccine hesitancy., Results: We included a total of 598 (about 60% women) participants. Little or no trust in the approved COVID-19 vaccines (aOR=2.28, 95% CI 1.24 to 4.20), lower perception of the importance of the vaccine on their personal health (5.26, 2.38 to 11.6), greater concerns about vaccine-related adverse effects (3.45, 1.83 to 6.47) and uncertainty about colleagues' acceptability of the vaccine (2.98, 1.62 to 5.48) were associated with higher odds of vaccine hesitancy. In addition, participants with chronic disease (aOR=0.34, 95% CI 0.12 to 0.97) and higher levels of concerns about getting COVID-19 (0.40, 0.18 to 0.87) were less likely to be hesitant to receive the COVID-19 vaccine., Conclusions: COVID-19 vaccine hesitancy among HCWs in this study was high and broadly determined by the perceived risk of COVID-19 and COVID-19 vaccines on personal health, mistrust in COVID-19 vaccines and uncertainty about colleagues' vaccine acceptability., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)