Among severely mentally ill (SMI) substance abusers, HIV rates are elevated and HIV risk reduction interventions have been shown to be less effective. An enhanced cognitive behavioral HIV risk reduction intervention (E-CB) for SMI was compared to a health promotion condition (HPC) in 222 psychiatric outpatients at 6 months postintervention. Compared to females, males in the E-CB improved on intention to practice safer sex and in condom use skills and in unprotected vaginal sex, but did not differ in HIV knowledge, perceived susceptibility, anxiety, condom attitudes, safer sex self-efficacy, unprotected vaginal sex acts, or sex partners. Across intervention groups, there were improvements in all areas except self-efficacy and number of partners. Risk reduction among SMI may be facilitated by increasing awareness of health related behaviors and HIV-targeted content. However, meaningful changes in critical risk reduction skills and intentions may require a more focused intervention and may vary by gender.