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To describe the burden of pediatric tuberculosis (TB) in a HIV-infected population and explore the demographic and clinical factors associated with the occurrence of pediatric TB.Longitudinal analysis of a cohort of HIV-infected children.The endpoint of the study was clinically diagnosed TB. Cox proportional hazard regression was used to explore the predictors of incident TB among HIV-infected children under age 15 years after enrollment into the HIV program.The cohort comprised of 5040 children [median age: 5 years, interquartile range (IQR) 1–9 years]. During a median follow-up of 0.8 (IQR 0.1–2.5) years, 376 out of 5040 children met the case definition for TB. The overall incidence of TB was 5.2/100 person-years. In multivariate analyses, older age at enrollment [relative risk (RR) 1.7, 95%, confidence interval (CI) 1.5–1.8], severe wasting (RR 1.8, 95% CI 1.3–2.5), severe immune suppression (RR 2.6, 95% CI 1.8–3.8), anemia (RR 1.4, 95% CI 1.0–1.9) and WHO stage IV (RR 4.5, 95% CI 2.4–8.5) were all independently associated with a higher risk of TB. In addition, the use of antiretroviral drugs for more than 180 days reduced the risk of TB by 70% (RR 0.3, 95% CI 0.2–0.4).Antiretroviral therapy (ART) use is strongly associated with a reduced risk of tuberculosis among HIV-infected children, and should therefore be included in HIV care and treatment programs. Trials of interventions designed to improve the nutritional and hematologic status of these children should also be performed.