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Abstract Background Vaccine efficiency has a significant role in the public perception of vaccination. The current study was designed to evaluate the efficacy of COVID-19 vaccines (AZD-1222, Sputnik-V, Sinopharm, and Covaxin) and the effect of gender on vaccine efficacy. We evaluated the efficacy of these vaccines among 214 health care employees in Iran. Blood samples were taken from all participants on day 0 and 14 days after the second dose. Humoral responses were evaluated by the PT-SARS-CoV-2-Neutralizing-Ab-96. Results The frequency of immunized individuals in the Sputnik V and AZD-1222 groups was 91% and 86%, respectively. This rate was 61% and 67% for Sinopharm and Covaxin vaccines. A comparison of the results obtained from the effectiveness of the vaccines between female and male groups did not demonstrate a significant difference. Conclusion According to the results, Sputnik V and AZD-1222 vaccines were more effective than Sinopharm and Covaxin vaccines. Moreover, the effectiveness of these vaccines is not related to gender.