Alanine aminotransferase (ALT) is commonly used to measure liver injury in resource-limited settings. Elevations in ALT are predictive of increased mortality from liver disease and may influence the choice of first-line antiretroviral therapy (ART). A cross-sectional analysis of the prevalence and predictors of elevated ALT (defined as >40 IU/L) was conducted. ART-naive, HIV-infected adults with a baseline ALT measurement who were enrolled in any of the 18 HIV Care and Treatment Clinics in Dar es Salaam, Tanzania between November 2004 and December 2009 were included in the study. Median values were calculated and log-binomial regression models were used to examine predictors of elevated ALT. During the study period, 41891 adults had a baseline ALT measurement performed. The prevalence of ALT >40, >120 and >200 IU/L was 13, 1 and 0.3%, respectively. In multivariate analyses, male sex, CD4 T lymphocyte count 40 IU/L (all P 130 mg/dL and current tuberculosis treatment were associated with a significantly reduced risk for elevated ALT. In this HIV-infected, ART-naive Tanzanian population, extreme elevations in ALT were infrequent but minor elevations were not uncommon. Antiretrovirals with potentially hepatotoxic side effects should be initiated with caution in male patients, and in patients with HBV coinfection, advanced immunosuppression and components of the metabolic syndrome.