Background: Perinatally HIV exposed uninfected (PHEU) adolescents are an increasing sub-population, especially in high HIV epidemic settings. HIV exposure may have some lasting implications for adolescents’ development, however, longer term health outcomes such as health risk behavior (HRB) are so far not well understood in this adolescent sub-population. Methods: In this systematic review, we identify the prevalent forms, burden, and underlying risk factors for HRB of PHEU adolescents. We searched in PubMed, PsycINFO and Applied Social Sciences Index & Abstracts for peer reviewed empirical studies published between 1980 and August 2018 on HRB among PHEU adolescents aged 10 – 19 years. Results: Eleven eligible studies, all conducted in North America were identified and they showed that sexual risk behavior such as lifetime unprotected sex increased drastically especially in mid-adolescence. PHEU adolescents’ substance use (especially alcohol and marijuana) was high and increased over time. In a significant minority (10-18%) substance use disorder was screened. Some intra and interpersonal risk factors such as caregiver and PHEU adolescents’ mental health problems, age and HIV status were shared across the two forms of HRB. However, other risk factors like race, gender and experience of traumatic life events were behavior specific. Conclusion: Overall, there is need to conduct similar research in other settings especially those with high HIV burden where the PHEU adolescent sub-population is rising. Future research in this area could benefit from examining more forms of HRB and exploring the clustering of HRB among PHEU adolescents.