Background: During a pandemic, healthcare workers are at high risk of contracting COVID-19. To protect these important individuals, it is highly recommended that they receive the COVID-19 vaccine. Our study focused on evaluating the safety and efficacy of Egypt’s first approved vaccine, the Sinopharm vaccine (BBIBP-CorV), and comparing these findings with other vaccines. Methods: An observational study was conducted in fifteen triage and isolation hospitals, from the 1st of March until the end of September 2021. The study included fully vaccinated and unvaccinated participants, and we measured vaccine effectiveness (using 1-aHR), the incidence rate of severely to critically ill hospitalized cases, COVID-19-related work absenteeism, and the safety of the vaccine as outcomes. Results: Of the 1364 healthcare workers who were interviewed, 1228 agreed to participate. After taking the hazard ratio into account, the vaccine effectiveness was found to be 67% (95% CI, 80–43%) for symptomatic PCR-confirmed cases. The incidence rate ratio for hospitalization was 0.45 (95% CI, 0.15–1.31) in the vaccinated group compared to the unvaccinated group, and there was a significant reduction in absenteeism among the vaccinated group (p< 0.007). Most adverse events were mild and well tolerated. Vaccinated pregnant and lactating mothers did not experience any sentinel adverse events. Conclusion: Our study found that the BBIBP-CorV vaccine was effective in protecting healthcare workers from COVID-19.