This paper describes an HIV prevention intervention designed in the US that was adapted and implemented in South Africa. Using an experimental design, 93 women who reported recent substance use and sex trading were randomly assigned to a modified Standard HIV intervention or to a Woman-Focused HIV prevention intervention. Eighty women completed the one-month follow-up interview. Participants reported high rates of sexual risk and violence at baseline. At follow-up, findings showed decreases in the proportion of women reporting unprotected sex and the daily use of alcohol and cocaine. Daily alcohol and cocaine use decreased more for women receiving the Woman-Focused intervention. Although violence continued to be a problem, at follow-up Woman-Focused participants reported being victimized less often than women receiving the Standard intervention. This study demonstrates the feasibility of implementing cross-cultural behavioral HIV prevention interventions, and supports the need for future studies of women's contextual issues and the effectiveness of targeted interventions.