The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (C max ) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median C max and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC 0 -8 ]) of INH (C max , 2.5 versus 5.1 g/ml, respectively [P ؍ 0.016]; AUC 0 -8 , 11.1 versus 22.0 g/ml · h, respectively [P ؍ 0.047[) and PZA (C max , 34.1 versus 42.3 g/ml, respectively [P ؍ 0.055]; AUC 0 -8 , 177.9 versus 221.7 g/ml · h, respectively [P ؍ 0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median C max of RMP (1.0 versus 2.8 g/ml, respectively; P ؍ 0.002) and PZA (31.9 versus 44.4 g/ml, respectively; P ؍ 0.045) were significantly lower. Among all factors studied, the PZA C max influenced TB treatment outcome (P ؍ 0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP C max . The PZA C max significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.