Importance: Although there are reports of COVID-19 vaccine implementation in real-world populations, these come from high-income countries or from experience with messenger RNA technology vaccines. Data on outcomes of vaccine deployment in low- or middle-income countries are lacking. Objective: To assess whether the pragmatic application of the 3 COVID-19 vaccines available in Argentina, 2 of which have no reports of evaluation in real-world settings to date, were associated with a reduction in morbidity, all-cause mortality, and mortality due to COVID-19. Design, Setting, and Participants: This cohort study used individual and ecological data to explore outcomes following vaccination with rAd26-rAd5, ChAdOx1, and BBIBP-CorV. To correct for differences in exposure times, results are shown using incidence density per 100 000 person-days from the start of the vaccination campaign (December 29, 2020) to the occurrence of an event or the end of follow-up (May 15, 2021). Participants included 663 602 people aged at least 60 years residing in the city of Buenos Aires, Argentina. Statistical analysis was performed from June 1 to June 15, 2021. Main Outcomes and Measures: Diagnosis of COVID-19 confirmed by reverse transcription-polymerase chain reaction, death from all causes, and death within 30 days of a diagnosis of COVID-19. Poisson regression models were fitted to estimate associations with all 3 outcomes. Results: Among 663 602 residents of the city of Buenos Aires included in the study, 540 792 (81.4%) were vaccinated with at least 1 dose, with 457 066 receiving 1 dose (mean [SD] age, 74.5 (8.9) years; 61.5% were female [n = 281 284]; 68.0% [n = 310 987] received the rAd26-rAd5 vaccine; 29.5% [n = 135 036] received ChAdOx1; 2.4% [n = 11 043] received BBIBP-CorV) and 83 726 receiving 2 doses (mean [SD] age, 73.4 [6.8] years; 63.5% were female [n = 53 204]). The incidence density of confirmed COVID-19 was 36.25 cases/100 000 person-days (95% CI, 35.80-36.70 cases/100 000 person-days) among those who did not receive a vaccine, 19.13 cases/100 000 person-days (95% CI, 18.63-19.62 cases/100 000 person-days) among those who received 1 dose, and 4.33 cases/100 000 person-days (95% CI, 3.85-4.81 cases/100 000 person-days) among those who received 2 doses. All-cause mortality was 11.74 cases/100 000 person-days (95% CI, 11.51-11.96 cases/100 000 person-days), 4.01 cases/100 000 person-days (95% CI, 3.78-4.24 cases/100 000 person-days) and 0.40 cases/100 000 person-days (95% CI, 0.26-0.55 cases/100 000 person-days). COVID-19-related-death rate was 2.31 cases/100 000 person-days (95% CI, 2.19-2.42 cases/100 000 person-days), 0.59 cases/100 000 person-days (95% CI, 0.50-0.67 cases/100 000 person-days), and 0.04 cases/100 000 person-days (95% CI, 0.0-0.09 cases/100 000 person-days) among the same groups. A 2-dose vaccination schedule was associated with an 88.1% (95% CI, 86.8%-89.2%) reduction in documented infection, 96.6% (95% CI, 95.3%-97.5%) reduction in all-cause death, and 98.3% (95% CI, 95.3%-99.4%) reduction in COVID-19-related death. A single dose was associated with a 47.2% (95% CI, 44.2%-50.1%) reduction in documented infection, 65.8% (95% CI, 61.7%-69.5%) reduction in all-cause death, and 74.5% (95% CI, 66%-80.8%) reduction in COVID-19-related death. Conclusions and Relevance: This study found that within the first 5 months after the start of the vaccination campaign, vaccination was associated with a significant reduction in COVID-19 infection as well as a reduction in mortality.