Background and Objective: Immunization is a protective measure against COVID‐19. This research aimed to estimate the association of protective levels of total IgG anti-S antibodies to SARS-CoV2 induced by vaccination and clinical and sociodemographic characteristics in a population of Cali, December 2021-February 2022.Study Design and Setting: A cross-sectional analytical study; 394 participants over 18 years with complete vaccination against COVID-19 were included. The antibodies were done by ELISA Immunoassay test. Multivariate analysis and logistic regression models were applied.Results: Protective antibody titers (≥ 1000 (BAU/mL) were reached by 282 participants. The variables associated were a) Type of vaccine aOR 2,40 (95% CI [0.99-5,84]) (p <0,053) for mRNA, against Inactivated viral vector vaccines users. b) Heterologous vaccination aOR 2.39 (95% CI [1.14-5.02]) (p < 0.021) and c) Time 21 days and more since the booster dose, aOR 2.62 (95% CI [1.29-5.30]) (p < 0.007), symptoms related to COVID-19 and age were not significant.Conclusions: The heterologous vaccination and the time after the last dose are important variables to predict the achievement of protective levels of antibodies against COVID-19, providing information to evaluate the performance of the immunization in Cali and highlighting these variables for future analysis.