To serve the unique needs of HIV-positive adolescents, an adolescent-focused HIV program, which included clinical, psychosocial, and community-based services, was established in rural Rwanda. From October 1, 2009, to February 1, 2011, 206 HIV-positive adolescents aged 11 to 19 years were enrolled, of whom 10 transferred care out of the program. Overall, 191 (97.5%) of 196 adolescents were retained, 4 (2%) were lost to follow-up, and 1 (0.5%) died. Median follow-up time was 4.6 (interquartile range 3.2 to 5.7) years. Among 124 patients on antiretroviral therapy (ART) for at least 1 year, median CD4 increase was 347 cells/mm3(36 to 553), and 87% achieved virologic suppression (<500 copies/mL). Clinic attendance was high, with 90.8% and 88.5% of ART-initiated and pre-ART patients, respectively, attending the clinic within 90 days of the end of the follow-up period. Our findings suggest that integrated, comprehensive, and youth-friendly clinics for HIV-positive adolescents can be successful in rural, resource-poor settings.