Drug induced hepatotoxicity is a recognized problem associated with the antiTuberculosis (anti-TB) chemotherapy and is of great concern in this era of HIV infection which has led to the resurgence of TB infection which hitherto was on the decline. Objectives: To obtain the prevalence of hepatotoxicity due to anti-TB medications in HIV positive and negative patients with pulmonary TB and to evaluate other possible risk factors for the development of hepatotoxicity. Method: This was a prospective case controlled study conducted on pulmonary TB patients with (cases) or without (controls) HIV co-infection attending the respiratory and Institute of Human Virology (IHV) clinics or admitted into the medical wards of the University of Benin Teaching Hospital (UBTH), Benin City. Two hundred and ninety four patients were enrolled for the study, of which 148 were HIV positive and 146 were HIV negative. Their liver function tests were done prior to commencement of therapy and they were followed up after 2 weeks, 4 weeks and 8 weeks. Hepatotoxicity was diagnosed using a serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >3 times the upper limit of normal (≤12 I.U/L) and/or total serum bilirubin of >25.5 µmol/L with or without symptoms. Results: One hundred and thirty two HIV positive patients and 129 HIV negative patients completed the study. Mean age of the cases was 35.32 ± 11.86 with range of 17 – 78 years and 84.8% belonging to the age range of 17 – 45 years, while the mean age of the controls was 34.29 ± 14.12 with range of 18 – 83 years and 81.4% in the age group of 17 – 45 years (P = 0.523). The cases comprised 47% females and 53% males while the controls were made up of 41.9% females and 58.1% males. Hepatotoxicity was observed in 15 patients (10 HIV positive and 5 HIV negative patients), giving a hepatotoxicity rate of 7.6% for HIV positive patients and 3.9% for HIV negative patients (P = 0.175). Age above 50 yrs (p = 0.001), female gender (p = 0.028), sputum positivity (p = 0.041), alcohol consumption (p = 0.018) and concomitant use of other drugs especially herbal preparations (p = <0.001) were found to be significant risk factors for hepatotoxicity. Also all patients with CD4 count <100 cells/mm3 developed hepatotoxicity (p = 0.020). Hepatitis B or C co-infection, HIV infection, BMI and PCV were not found to be significant risk factor for hepatotoxicity. Conclusion: Anti-TB drug induced hepatotoxicity is not uncommon and tends to occur more in HIV positive persons than in HIV negative persons, though the difference in prevalence is not statistically significant. The severity of immunosuppression, age above 50 yrs, female gender, the use of concomitant herbal concoction and alcohol consumption increased the risk of hepatotoxicity among HIV positive persons. Early recognition and prompt discontinuation of treatment, especially in HIV positive patients and those with risk factors will help reduce the mortality associated with this conditio