The major purpose of this article is to systematically review and synthesise empirical findings from selected adolescent STI/HIV interventions conducted in the United States between 1994 and 2004. Specifically, the most current adolescent STI risk reduction interventions conducted in diverse venues, such as in the community, schools, clinics, and specialised adolescent centres (that is, detention homes and drug programmes) were examined for reported efficacy, and were assessed for programmatic and methodological strengths and weaknesses. Next, a subset of programmatic characteristics was identified that were associated with the efficacy of STI risk reduction programmes both within a particular venue, as well as across all venues. Finally, we discuss the research and practice implications of these findings for optimising future evidence based STI risk reduction programmes for adolescents in the United States.