Background In February 2021, Colombia began mass vaccination against COVID-19 using mainly BNT162b2 and CoronaVac vaccines. We aimed to estimate vaccine effectiveness (VE) to prevent COVID-19 symptomatic cases, hospitalization, critical care admission, and deaths in a cohort of 796,072 insured subjects older than 40 years in northern Colombia, a setting with a high SARS-CoV-2 transmission. Methods We identified individuals vaccinated between March 1st of 2021 and August 15th of 2021. We included symptomatic cases, hospitalizations, critical care admissions, and deaths in patients with confirmed COVID-19 as main outcomes. We calculated VE for each outcome from the hazard ratio in Cox proportionally hazards regressions (adjusted by age, sex, place of residence, diabetes, human immunodeficiency virus, cancer, hypertension, tuberculosis, neurological diseases, and chronic renal disease), with 95% confidence intervals (CI). Findings A total of 719,735 insured participants of 40 and more years were followed. We found 21,545 laboratoryconfirmed symptomatic COVID-19 among unvaccinated population, along with 2874 hospitalizations, 1061 critical care admissions, and 1329 deaths, for a rate of 207.2 per million person-days, 27.1 per million person-days, 10.0 per million person-days, and 12.5 per million person-days, respectively. We found CoronaVac was not effective for any outcome in subjects above 80 years old; but for people 40-79 years of age, we found two doses of CoronaVac reduced hospitalization (33.1%; 95% CI, 14.5−47.7), critical care admission (47.2%; 95% CI, 18.5−65.8), and death (55.7%; 95% CI, 32.5−70.0). We found BNT162b2 was effective for all outcomes in the entire population of subjects above 40 years of age, significantly declining for subjects ≥80 years. Interpretation Two doses of either CoronaVac in population between 40 and 79 years of age, or BNT162b2 among vaccinated above 40 years old significantly reduced deaths of confirmed COVID-19 in a cohort of individuals from Colombia. Vaccine effectiveness for CoronaVac and BNT162b2 declined with increasing age. Funding UK National Institute for Health Research, the European Union’s Horizon 2020 research and innovation programme, and the Bill & Melinda Gates Foundation.