We aimed to compare vaccinated and unvaccinated patients hospitalized with COVID-19 in terms of disease severity, need for intensive care unit (ICU) admission, and death. In addition, we determined the factors affecting the COVID-19 severity in vaccinated patients. Patients aged 18–65 years who were hospitalized for COVID-19 between September and December 2021 were retrospectively analyzed in three groups: unvaccinated, partially vaccinated, and fully vaccinated. A total of 854 patients were included. Mean age was 47.9 ± 10.6 years, 474 patients (55.5%) were male. Of these, 230 patients (26.9%) were fully vaccinated, 97 (11.3%) were partially vaccinated, and 527 (61.7%) were unvaccinated. Of the fully vaccinated patients, 67% (n = 153) were vaccinated with CoronaVac and 33% (n = 77) were vaccinated with Pfizer-BioNTech. All patients (n = 97) with a single dose were vaccinated with Pfizer-BioNTech. One hundred thirteen (13.2%) patients were transferred to ICU. A hundred (11.7%) patients were intubated and 77 (9.0%) patients died. Advanced age (P = 0.028, 95% CI = 1.00–1.07, OR = 1.038) and higher Charlson Comorbidity Index (CCI) (P < 0.001, 95% CI = 1.20–1.69, OR = 1.425) were associated with increased mortality, while being fully vaccinated (P = 0.008, 95% CI = 0.23–0.80, OR = 0.435) was associated with survival in multivariate analysis. Full dose vaccination reduced the need for ICU admission by 49.7% (95% CI = 17–70) and mortality by 56.5% (95% CI = 20–77). When the fully vaccinated group was evaluated, we found that death was observed more frequent in patients with CCI>3 (19.1 vs 5.8%, P < 0.01, OR = 3.7). Therefore, the booster vaccine especially in individuals with comorbidities should not be delayed, since the survival expectation is low in patients with a high comorbidity index.