OBJECTIVE To estimate the rate of optimal response to antiretroviral therapy and its predictors in Colombia. METHODS A retrospective cohort study was performed. The medical records of all patients at three major HIV clinics in different areas of Colombia, South America, were reviewed. Eligible patients met the following criteria: (1) viral load test available while on therapy; and (2) patients must have been on a stable first antiviral regimen for at least 1 year (48 weeks). Optimal virologic response was defined as a viral load <400 copies/ml. RESULTS Two hundred and twenty patients were eligible for the study. The optimal virologic response rate was 40% (95% confidence interval 34-46%). Younger age (p=0.02) and western region of the country (p=0.026) were the only significant predictors of non-optimal response in bivariate analysis. Multivariate logistic regression analysis confirmed younger age (p=0.0054) and geographic area (p=0.0468) as independent predictors of non-optimal response. CONCLUSIONS The optimal response rate in some areas of Colombia seems lower than that reported for other areas of the developing world. Poorer virologic responses were observed in younger patients and in those from the western region of the country.