Objective: Studies on the association of the aspartate transaminase-to-alanine transaminase ratio with the metabolic syndrome and its components among HIV patients were scarce. This study aims to determine the association between the aspartate transaminase-to-alanine transaminase ratio and the metabolic syndrome and its components in adult HIV patients on highly active antiretroviral therapy. Methods: This was a cross-sectional study conducted on 302 HIV patients from January 15 to June 30, 2021. Sociodemographic, clinical, and anthropometric data were collected using a structured questionnaire. The patient’s medical records were reviewed. Biochemical analysis was performed after 5 ml of venous blood was collected from each study participant. Metabolic syndrome was defined by the third report of the national cholesterol education program-adult treatment panel. Logistic regression was done to assess the association of MetS with the independent variables, and correlation analysis was performed to see the correlation of MetS components with the aspartate aminotransferase-to-alanine aminotransferase ratio. Result: 302 HIV—positive patients on highly active antiretroviral therapy were included in this study, and 54.6% were female. The median and interquartile range of the age of the study participants were 41 (35–50) years. The prevalence of metabolic syndrome was 29.5% (confidence interval = 24.5–35.1). Chronic illness (Adjusted odds ratio = 4.8, confidence interval = 2.2–10.9) and aspartate aminotransferase-to-alanine aminotransferase ratio (adjusted odds ratio = 2.5, confidence interval = 1.4–4.4) were significantly associated with Metabolic syndrome among the study participants. The aspartate aminotransferase-to-alanine aminotransferase ratio was significantly correlated with blood pressure. Conclusion: This study found the existence of a significant association between the aspartate aminotransferase-to-alanine aminotransferase ratio and metabolic syndrome among HIV patients.