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Introduction: COVID-19 is an infectious and contagious disease declared as public health emergency of international concern in 2020. Given its high morbidity and mortality, one of the responses to this pandemic is vaccination, which has posed a serious problem of acceptance among the population in sub-Saharan Africa (SSA) and Cameroon in particular. Thus, the purpose of this study was to contribute to a better response to the pandemic in Cameroon by measuring the effectiveness of the COVID-19 vaccine. We carried out a comparative analysis of morbidity and mortality in vaccinated COVID-19 patients versus unvaccinated COVID-19 patients hospitalized in the three most affected regions of Cameroon., Methods: we conducted a Case-control study with patients vaccinated against COVID-19 as Cases and patients not vaccinated against COVID-19 as controls. We observed the occurrence of severe clinical manifestations in vaccinated and unvaccinated COVID-19 patients during hospitalization to study the influence of vaccination on the outcome of these patients over the period from May 01, 2021, to March 31, 2022; in the COVID management units of Yaoundé Central Hospital, Douala General Hospital, Douala Laquintinie Hospital and Bafoussam Regional Hospital., Results: we conducted our study in 218 hospitalized COVID-19 patients, 109 vaccinated and 109 unvaccinated patients, 51.4% of whom were women. Arterial hypertension (60.6%) and diabetes (27.5%) were more prevalent in unvaccinated patients. The median length of hospital stay was 07 days for vaccinated patients and 05 days for unvaccinated patients. Coma (0.7% in vaccinated patients and 79.8% in unvaccinated patients), consciousness disorders (8.3% in vaccinated patients and 57.8% in unvaccinated patients), headaches (46.8% in vaccinated patients and 18.3% in unvaccinated patients), pneumonia (78% in vaccinated patients and 78.9% in unvaccinated patients), malaria (31.2% in vaccinated patients and 19.3% in unvaccinated patients), pulmonary embolism (14.7% in vaccinated patients and 22% in unvaccinated patients) and venous thromboembolism (1.1% in vaccinated patients and 14.7% in unvaccinated patients) were the main severe clinical manifestations. The prevalence of mortality was 1.8% in vaccinated patients and 79.8% in unvaccinated patients., Conclusion: four out of 1000 vaccinated patients were less likely to die during hospitalization compared to unvaccinated patients. This reinforces the importance of vaccination in controlling COVID-19 infection., Competing Interests: Les auteurs ne déclarent aucun conflit d'intérêts., (Copyright: Jean Yves Bevela et al.)