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Retention of participants in clinical trials is a central concern of HIV/STI behavioral researchers and research sponsors. This article describes the strategies used for addressing the challenges in retaining South African adolescents for a 54-month longitudinal study. The objective of the South African adolescent health promotion long-term follow-up trial was to test the sustainability of the effects of an HIV/STI risk reduction intervention, "Let Us Protect Our Future," on young adolescents as they aged into middle and late adolescence. Inaccurate contact information, invalid mobile telephone numbers, lack of transportation, transitory family addresses, and family relocation were among the challenges to retaining participants. Despite a significant gap in time of 36 months between the main trial and the long-term follow-up study, 99.2% of 1057 participants were retained. Solutions used for retaining the adolescents are discussed with suggestions offered for retaining adolescents in longitudinal HIV/STI prevention clinical trials in low resource countries.