The purpose of the current study is to investigate the association between vaccination status and clinical outcomes in the elderly during the Omicron wave. A total of 1 029 patients aged 60 years or older were hospitalized in Huashan Hospital of Fudan University, Baoshan Campus from March 20 to May 6, 2022 (643 cases unvaccinated, 386 cases vaccinated). Demographic characteristics, clinical symptoms, laboratory findings, and clinical outcomes were compared, and multivariate regression was applied to determine association between vaccination status and clinical outcomes. Results indicated a significant difference in age, BMI, comorbidity (diabetes, cardiovascular disease, chronic kidney disease), number of comorbidities, and laboratory findings (lymphocyte counts, C-reactive protein, D-dimer, ALT, creatinine, pro-BNP and troponin) between unvaccinated and vaccinated patients (P<0.05). Unvaccinated patients were more likely to experience COVID-19-related outcomes, including pneumonia (51.6% vs 26.2%), respiratory support [40.7% vs 13.5%], invasive ventilation or death [6.2% vs 0.7%]. Multivariate regression analysis showed that vaccination was associated with early virus shedding [aHR＝1.594, 95%CI (1.259, 2.017)], and protected against progression to pneumonia [aOR＝0.501, 95%CI (0.370, 0.678)], respiratory support [aOR＝0.336, 95%CI (0.232, 0.487)], invasive ventilation or death [aOR＝0.190, 95%CI (0.052, 0.687)] in elderly patients. Our findings suggest that inactivated vaccine protects against COVID-19-related severe outcomes in individuals aged over 60 years.