Existing evidence-based HIV risk reduction interventions have not been designed for implementation within clinical settings, such as methadone maintenance programs, where many high-risk drug users seek treatment services. We therefore systematically developed an adapted, significantly shortened, version of a comprehensive evidence-based intervention called the Community-friendly Health Recovery Program (CHRP) which has demonstrated preliminary evidence of efficacy in a feasibility/acceptability study already published. In a randomized controlled trial reported here, we tested the efficacy of the CHRP intervention among high-risk drug users newly enrolled in drug treatment at an inner-city methadone maintenance program. The CHRP intervention produced improvements in drug risk reduction knowledge as well as demonstrated sex- and drug-risk reduction skills. Support was found for the IMB model of health behavior change. Implications for future intervention research and practice are considered.