COVID-19, caused by SARS-CoV-2 infection, left widespread impacts worldwide. In Brazil, immunization reduced incidence rates. However, six months later, waning neutralizing antibody titers and new immune-evading variants increased cases, resulting in recurring waves. This study evaluated hospitalized COVID-19 patients after the vaccination rollout, comparing the clinical outcomes between vaccinated and unvaccinated patients. Positive samples underwent nucleotide sequencing. A total of 218 patients were included; 202 (92 %) had vaccination data, 98 received at least one dose, and 64 completed the vaccination schedule, predominantly with CoronaVac®. Vaccinated individuals were older on average since the campaign was primarily conducted among the elderly. The Gamma variant predominated during the study period. While not statistically significant, trends indicated greater respiratory assistance needs, more extended hospital stays, and increased ICU time among unvaccinated patients. Mortality was 45 % in vaccinated and 37 % in unvaccinated groups, with no notable difference. However, patients with a complete vaccination schedule showed a higher chance of survival, though not significant (p = 0.11). The factors significantly associated with higher mortality were older patients, those requiring vasopressor drugs, and mechanical ventilation. These findings provide clinical, epidemiological, and phylogenetic insights into COVID-19 patients during vaccination implementation. They underscore the need to evaluate vaccine effectiveness against circulating variants and highlight the importance of complete vaccination schedules for improving patient outcomes.