This investigation compared the effectiveness of a cognitive-behavioral HIV risk reduction intervention with a standard care (SC) comparison condition in modifying HIV risk related knowledge, beliefs, attitudes, and behavior at 6-month and 12-month follow-ups among 149 HIV seronegative males. The two intervention conditions were administered while participants were in inpatient alcohol and other drug abuse treatment. Global drug abuse severity, as well as injection drug abuse, decreased significantly from preintervention to follow-up across conditions. There were significant increases in the proportions reporting sexual activity and increases in levels of unprotected sex acts between baseline and follow-up across conditions. However, no changes in sex risk behavior were found among those who reported sexual activity both prior to and after intervention across conditions. Participants revealed relatively adequate knowledge regarding HIV and HIV risk reduction practices, strong belief in the utility of safer practices and in their ability to enact such practices, and relatively strong commitment to practice safer sex across conditions at baseline assessment. In general, substantial postintervention improvements over baseline levels in these areas were not found. Relatively modest changes in sexual self-efficacy and in safe-sex guidelines were identified in analyses involving the total sample. Exploratory subgroup analysis suggested increases in knowledge and reductions in susceptibility and anxiety among those who reported sexual activity both prior to and after intervention. Among participants reporting initiation of sexual activity after intervention, those receiving SC revealed changes in perceived susceptibility and in condom attitudes. A discussion is presented of challenges associated with providing meaningful HIV risk reduction intervention when baseline levels of sex risk behavior, perceived HIV infection susceptibility, and HIV anxiety are only moderate and when initial levels of sexual self-efficacy and commitment are relatively high.