BACKGROUND: Efforts to scale-up HIV treatment in high burden countries have resulted in wider access to care, improved survival and decreased morbidity for HIV-infected children. The country of Rwanda has made significant achievements in expanding coverage of pediatric HIV services. METHODS: We describe the extent of and factors associated with mortality and lost to follow-up (LTF) in children (<15 years) enrolled in HIV care at 39 ICAP-supported facilities across Rwanda from 2004 to 2010 by antiretroviral treatment (ART) status. We estimated the 1-year cumulative incidence of death and LTF among all children enrolled in care (pre-ART) and children on ART. Survival analysis was used to evaluate factors associated with death and LTF in both groups. RESULTS: Between January 2004 and June 2010, 3244 children with a median age of 5.7 years (interquartile range 2.8-9.6) enrolled in HIV care. One-year cumulative incidence for death and LTF among pre-ART children was 4% (95% confidence interval [CI]: 3-5%) and 5% (95% CI: 4-6%), respectively. Overall, 2035 (63%) children initiated ART, median age 6.3 years (interquartile range 3.3-10.4): 1-year Kaplan-Meier estimates of death and LTF were 3% (95% CI: 3-4%) and 1% (95% CI: 1-2%), respectively. Factors associated with an increased hazard for death among pre-ART children included being <18 months old versus ≥5 years (adjusted sub hazard ratio [aSHR] = 4.4, 95% CI: 2.9-6.8) and World Health Organization stage IV versus I (aSHR = 4.1, 95% CI: 2.0-8.4), whereas children entering care through prevention of mother-to-child transmission had lower hazard than those from voluntary counseling and testing (aSHR = 0.50, 95% CI: 0.25-1.0). Markers of advanced disease, including severe immunosuppression (aSHR = 0.25, 95% CI: 0.12-0.54), and enrollment in care in rural versus urban clinics (aSHR = 0.71, 95% CI: 0.53-0.97) were protective against LTF. For children on ART, factors associated with hazard of death included younger age (adjusted hazard ratio [aHR] <18 months versus ≥5 years = 2.1, 95% CI: 1.3-3.6), severe malnutrition versus not malnourished (aHR = 3.2, 95% CI: 1.3-8.1), advanced World Health Organization stage (aHR IV versus I = 9.8, 95% CI: 3.5-27.4) and severe immunodeficiency versus no evidence (aHR = 2.3, 95% CI: 1.7-3.3). No associations were observed with LTF among children on ART. CONCLUSIONS: The results demonstrate very high retention among children enrolled in HIV care in Rwanda. Younger children continue to be particularly vulnerable, underscoring the urgent need for early identification, rapid treatment initiation and long-term retention in care.