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HIV/AIDS is still a major killer disease among adolescents in sub- Saharan Africa and Uganda in particular. There are many factors attributed to high HIV infections among young people in Uganda such as, multiple sexual partners, low condom use, those born with HIV and poverty. High level misinformation in the indigenous knowledge related to sexuality and HIV prevention remains an under investigated and under documented factor escalating the disease. Yet, the indigenous knowledge health information system is a major critical information source adolescents depend on for health information on HIV prevention in Uganda. Indigenous knowledge informs health interventions for HIV prevention among young people in many African communities and is relied on for decision making on health choices. This paper documents indigenous knowledge on practices for HIV prevention among secondary school adolescents in an urban context in Kampala District. A qualitative case study research design was employed. The findings revealed use of witchcraft, local herbs, male circumcision, elongation of labia menorah, abstinence, sexual taboos like not having sex with women in their menstrual periods and avoiding homosexuality as the key indigenous management practices for HIV prevention. Some of the findings were in agreement with existing biomedical information on prevention strategies while others were in contradiction. The findings also revealed that adolescents have a lot of misinformation on HIV prevention; such information may not support right healthy choices. The study contributes to the body of existing knowledge on HIV prevention using indigenous knowledge practices. The findings appeal to information science professionals to participate in ensuring that communities they serve have access to accurate and timely information to curb health emergencies and improve on health of societies they serve.