Background: Few Indian studies have reported the long-term efficacy of anti-retroviral treatment (ART) in children and in orphaned, HIV-infected children in particular.Aim: To study differences in outcome of ART in HIV-infected orphans compared with non-orphans.Methods: A retrospective study of 87 HIV-infected children who commenced ART in the period January 2006 to August 2007. The main measures were orphan status, absolute CD4 count and weight-for-height (WHZ) and height-for-age (HAZ) Z-scores.Results: Median follow-up was 33 months. Forty (45·9%) children were orphaned. Orphans and non-orphans had similar baseline median WHZ and HAZ (−2·48 vs −2·63, P = 0·65 and −2·78 vs −2·91, P = 0·77, respectively). The two groups were similar in terms of WHO clinical stage and frequency of severe immunosuppression at presentation (P = 0·88 and 0·25, respectively). After ART initiation, the median absolute CD4 count increased progressively in both groups. Median WHZ and HAZ increased throughout the study period in the orphans and reached −1 at 27 and 39 months of ART, respectively. In the non-orphans, WHZ remained below that of the orphan group, the difference becoming statistically significant from 18 months of ART. The increment in HAZ in the non-orphan group was at par with the orphan group until 12 months of follow-up, after which it fell between 18 and 30 months. Subsequently, HAZ rose but remained below that of the orphan group. Both WHZ and HAZ failed to reach −1 in the non-orphan group. In both groups, 85% reported 100% adherence to ART.Conclusion: The outcome of ART is not affected by orphan status with the extended family adequately supporting orphaned children. Growth of children whose parents are HIV-infected may be constrained despite ART if there is inadequate family support.