Combination antiretroviral therapy (ART) has been used for HIV-infected children in many Asian countries since 2002. This study describes survival outcomes among HIV-infected children in a multicenter regional cohort in Asia. Retrospective and prospective data collected through March 2009 from children in 5 countries enrolled in TREAT Asia's Pediatric HIV Observational Database were analysed. Multivariate Cox proportional hazard models were used to assess factors associated with mortality in children who received ART. Among 2280 children, 1752 (77%) had received ART. During a median follow-up of 3.1 years after ART, 115 (6.6%) deaths occurred, giving a crude mortality rate of 1.9 per 100 child-years [95% confidence interval (CI): 1.6 to 2.4]. The mortality rate was highest in the first 3 months of ART (10.2 per 100 child-years; 95% CI: 7.5 to 13.7) and declined after 12 months (0.9 per 100 child-years; 95% CI: 0.7 to 1.3). Those with a low recent CD4 percentage, who started ART with lower baseline weight-for-age Z score, or with WHO clinical stage 4 had an increased risk of death. Of 528 (23%) children who never received ART, 36 (6.8%) died after presenting to care, giving a crude mortality rate of 4.1 per 100 child-years (95% CI: 3.0 to 5.7), with a lost-to-program rate of 31.5 per 100 child-years (95% CI: 28.0 to 35.5). The high mortality during the first 3 months of ART and in those with low CD4 percentage support the implementation of early diagnosis and ART initiation.