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Vaccination remains the most effective way to prevent COVID-19. The aim of the present study was to assess the incidence of COVID-19 hospitalizations after vaccination, as well as the effect of prior vaccination on hospitalization outcomes among patients with COVID-19. We analyzed and compared all consecutive patients, with or without prior vaccination, who were admitted to our hospital network due to COVID-19 from January to April 2021. Our primary outcome was to identify and describe cases of COVID-19 hospitalized after vaccination. We also utilized a multivariate logistic regression model to investigate the association of previous vaccination with hospitalization outcomes. We identified 915 consecutive patients hospitalized due to COVID-19 with 91/915 (10%) previously vaccinated with at least one dose of a COVID-19 vaccine. Utilizing our multivariate logistic regression model, we found that prior vaccination, regardless of the number of doses or days since vaccination, was associated with decreased mortality (aOR 0.44, 95% CI: 0.20–0.98) when compared to unvaccinated individuals. Our study showed that COVID-19 related hospitalization after vaccination may occur to a small percentage of patients, mainly those who are partially vaccinated. However, our findings underline that prior vaccination, even when partial, is associated with a decreased risk of death. Ongoing vaccination efforts should remain an absolute priority.