SummaryObjectivesTo assess the determinants of COVID-19 vaccine acceptance and hesitation among Health Care Professionals (HCPs) in the Kintampo North Municipality of Ghana.DesignAn analytical cross-sectional study.SettingThe study was carried out in the Kintampo North Municipality.ParticipantsAll health care professionals within the Kintampo North Municipality of Ghana.Main outcome measureAcceptance of COVID-19 vaccine.ResultsIn all, 215 HCPs were included in this study. The overall vaccine acceptance was 78.6% among HCPs, while 21.4% were hesitant to receive the COVID-19 vaccine. Majority (57.7%) of HCPs believed that COVID-19 vaccines were safe. The following factors were found to influence vaccine acceptance significantly; those who knew someone who has taken the vaccine (adjusted Odds Ratio [aOR]; 14.9, 95% Confidence Interval [95% CI];5.0–45.0, p<0.001), those who think COVID -19 vaccine in Ghana was safe (AOR;9.2, 95%CI;3.3–25.8, P<0.001), those who said vaccines are effective in controlling COVID-19 transmission (aOR=5.0, 95%CI;2.1–12.4, p<0.001), and those who have never refused vaccines in the past (aOR=7.8, 95CI;1.6–37.8, p=0.01).ConclusionThe study indicated high COVID-19 vaccination acceptability among HCPs. However, some HCPs are hesitant to take COVID-19 vaccinations immediately. Increased adoption of COVID-19 vaccinations among HCPs and the broader Ghanaian population requires concerted efforts, including strengthening public health education on the perceived risks and safety of COVID-19 vaccines.FundingNone declared