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 = 0.001) and self efficacy to discuss HIV and sex with men (p less than 0.001) and with boys (p less than 0.001). Responses to items about social norms of HIV risk behavior were also somewhat improved (p = 0.09). 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.