Background Low retention of HIV-positive adolescents in care is a major problem across HIV programs. Approximately 70% of adolescents were nonretained in care at Katooke Health Center, Mid-Western Uganda. Consequently, a quality improvement (QI) project was started to increase retention from 29.3% in May 2016 to 90% in May 2017. Methods In May 2016, we analyzed data for retention, prioritized gaps with theme-matrix selection, analyzed root causes with fishbone diagram, developed site-specific improvement changes and prioritized with countermeasures matrix, and implemented improvement changes with Plan-Do-Study-Act (PDSA). Identified root causes were missing follow-up strategy, stigma and discrimination, difficult health facility access, and missing scheduled appointments. Interventions tested included generating list of adolescents who missed scheduled appointments, use of mobile phone technology, and linkage of adolescents to nearest health facilities (PDSA 1), Adolescent Only Clinic (PDSA 2), and monthly meetings to address care and treatment challenges (PDSA 3). Results Retention increased from 17 (29.3%) in May 2016 to 60 (96.7%) in August 2016 and was maintained above 90% until May 2017 (with exception of February and May 2017 recording 100% retention levels). Conclusion Context specific, integrated, adolescent-centered interventions implemented using QI significantly improved retention in Mid-Western Uganda.