We adapted a U.S. HIV prevention program to address knowledge gaps and cultural pressures that increase the risk of infection in adolescent Ghanaian girls. The theory-based nine-module HIV prevention program combines didactics and games, an interactive computer program about sugar daddies, and tie-and-dye training to demonstrate an economic alternative to transactional sex. The abstinence-based study was conducted in a church-affiliated junior secondary school in Nsawam, Ghana. Of 61 subjects aged 10-14 in the prevention program, over two thirds were very worried about becoming HIV infected. A pre-post evaluation of the intervention showed significant gains in three domains: HIV knowledge (p = .001) and self efficacy to discuss HIV and sex with men (p < .001) and with boys (p < .001). Responses to items about social norms of HIV risk behavior were also somewhat improved (p = .09). Subjects rated most program features highly. Although short-term knowledge and self-efficacy to address HIV improved significantly, longer term research is needed to address cultural and economic factors placing young women at risk of HIV infection.