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Objective: We carried out a study to estimate the vaccine effectiveness (VE) of homologous vaccination schedules against COVID-19, using data from mandatory information systems from Bogota, Colombia., Methods: A test-negative case-control study in adults from Bogota (Colombia), between March 1st of 2021 and February 25th of 2022. We assess VE among symptomatic COVID-19 cases during the Mul, Delta, and Omicron predominance periods in Bogota, with controls matched by sex, age (±5 years), and date of testing (±7 days), using a case:control ratio of 1:1. We selected homologous vaccination schedules with ChAdOx1, CoronaVac, BNT162b2, mRNA-1273, and Ad26.COV2.S. VE was reported as one minus the odds ratio in adjusted conditional logistic regressions, with their 95% confidence intervals (CI). A p-value < 0.05 was considered statistically significant., Results: 52,913 cases were matched to controls, 16,722 for Mu, 14,094 for Delta, and 22,097 for Omicron. VE was high against COVID-19 during Mu weeks with full vaccination using the monovalent BNT162b2 (VE: 69; 95% CI, 65 to 72) vaccine and ChAdOx1 (VE: 64; 95% CI, 31 to 81) and significantly lower with CoronaVac (P < 0.001) and Ad26.COV2.S (P = 0.005). During Delta, VE against COVID-19 was higher with BNT162b2 (VE: 55; 95% CI, 51 to 58). The VE for COVID-19 cases during Omicron was higher with a booster dose of monovalent BNT162b2 (VE: 45; 95% CI, 34 to 54). The VE of primary series and booster for ChAdOx1, Ad26.COV2.S, and CoronaVac did not show protection for Omicron., Conclusion: Our study provides further evidence on the protective effect of mRNA vaccines for Omicron, and warrant that the duration of protection against symptomatic infection may last for only a few months., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nelson Alvis-Zakzuk reports a relationship with Pfizer that includes: consulting or advisory and funding grants. Lina Moyano reports a relationship with Pfizer that includes: consulting or advisory., (Copyright © 2023 Elsevier Ltd. All rights reserved.)