This study examined gender differences in the rates and correlates of HIV risk behaviors among 1,429 clients participating in multi-site trials throughout the United States between 2001 and 2005 as part of the National Institute on Drug Abuse-funded Clinical Trials Network. Women engaged in higher risk sexual behaviors. Greater alcohol use and psychiatric severity were associated with higher risk behaviors for women, while impaired social relations were associated with decreased risk for men. Specific risk factors were differentially predictive of HIV risk behaviors for women and men, highlighting the need for gender-specific risk-reduction interventions. Limitations of the study are discussed.