Objectives: The second wave of coronavirus disease 2019 (COVID-19) cases in Indonesia, during which the Delta variant predominated, took place after a vaccination program had been initiated in the country. This study was conducted to assess the impact of COVID-19 vaccination on unfavorable clinical outcomes including hospitalization, severe COVID-19, intensive care unit (ICU) admission, and death using a real-world model. Methods: This single-center retrospective cohort study involved patients with COVID-19 aged ≥18 years who presented to the COVID-19 emergency room at a secondary referral teaching hospital between June 1, 2021 and August 31, 2021. We used a binary logistic regression model to assess the effect of COVID-19 vaccination on unfavorable clinical outcomes, with age, sex, and comorbidities as confounding variables. Results: A total of 716 patients were included, 32.1% of whom were vaccinated. The elderly participants (≥65 years) had the lowest vaccine coverage among age groups. Vaccination had an effectiveness of 50% (95% confidence interval [CI], 25 to 66) for preventing hospitalization, 97% (95% CI, 77 to 99) for preventing severe COVID-19, 95% (95% CI, 56 to 99) for preventing ICU admission, and 90% (95% CI, 22 to 99) for preventing death. Interestingly, patients with type 2 diabetes had a 2-fold to 4-fold elevated risk of unfavorable outcomes. Conclusions Among adults, COVID-19 vaccination has a moderate preventive impact on hospitalization but a high preventive impact on severe COVID-19, ICU admission, and death. The authors suggest that relevant parties increase COVID-19 vaccination coverage, especially in the elderly population.