Abstract: Background and Objective: There is increased awareness in the use of antiretroviral therapy. However, these drugs are to be considered along with their potential adverse effects. Some of these adverse effects which may be hepatotoxic may be associated with the duration of treatment. The study was, therefore, designed to compare duration of treatment of antiretroviral drugs with the selected liver enzymes. Materials and Methods: This research was conducted on 276 patients who were HIV positive. Data of patients who finally satisfied the inclusion criteria were analyzed. Aspartate aminotransaminase, ALT and ALP were determined by the use of commercial kits manufactured by Randox Laboratory, Alden, the USA on plasma extracted from an aseptically collected blood sample from each subject. Results: There were statistically significant differences (ALT p<0.001, ALP p<0.001) in the mean values of ALT (male, 30.61±20.63, female, 20.70±15.67) and ALP (male, 15.42±8.14, female, 11.06±7.17) between genders. There were no significant differences observed in the enzymes when duration of therapy was considered. However, the mean values of these enzymes were higher in patients who had taken medication for less than 5 years than those who had taken for more than 5 years. Conclusion: There were no statistically significant differences in plasma AST, ALT and ALP in patients on antiretroviral therapy when linked to the duration of treatment. However, non-significant raised values of these enzymes in patients who had taken medication for less than 5 years should not be overlooked.