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Few studies have directly compared response to antiretroviral therapy (ART) between children living in well-resourced and resource-limited settings. In resource-limited settings non-HIV contributors could reduce the beneficial effects of ART. We compare predictors of short-term immunological, virological, and growth response to ART in HIV-infected children in the United Kingdom/Ireland and Kampala.We analyzed prospective cohort data from 54 UK/Irish hospitals (the Collaborative HIV Paediatric Study) and Mulago Hospital, Kampala, Uganda. Six- and 12-month responses are described among children initiating combination ART (≥3 drugs, ≥2 classes). Six months post-ART, predictors of viral load (VL) suppression <400 copies/mL, CD4% increases >10%, and height- and weight-for-age z-score increases ≥+0.5 were investigated using logistic regression.In all, 582 UK/Irish children (76% black African) were younger than 876 Kampala children at ART initiation (median 5.0 vs 7.6 years), with higher CD4% (14%, 8%), lower VL (172,491 and 346,809 copies/mL), and less stunting (−0.8, −2.8) and wasting (−0.6, −2.8). Post-ART, median 12-month changes in the United Kingdom/Ireland and Kampala in CD4% (+12%, +13%) and weight (+0.4, +0.5) were similar, but growth was less in Kampala (+0.20, +0.06, P < 0.001). Younger children in both cohorts had better immunological, weight, and growth responses (all P < 0.001). However, lower pre-ART CD4% predicted better immunological response in the United Kingdom/Ireland but poorer response in Kampala (heterogeneity P = 0.004). Although 70% children in both cohorts had suppressed <400 copies/mL at 6 months, adolescents starting ART in the United Kingdom/Ireland had somewhat poorer VL responses than those in Kampala (P = 0.15).Overall immunological and virologic ART responses were similar in children in both cohorts. Poorer CD4 recovery in more immunosuppressed Kampala children and blunted growth responses likely reflect higher background malnutrition and infection rates in Uganda, suggesting the need for earlier HIV diagnosis, nutritional support, cotrimoxazole prophylaxis, and ART.