Background: Behavioral medicine and public health prevention are moving rapidly towards using evidence-based practices. Consistent with this movement, the Centers for Disease Control and Prevention (CDC) emphasizes the use of the current and best scientific evidence in making policy and programmatic decisions for HIV prevention. The CDC’s Division of HIV/AIDS Prevention (DHAP) developed a Research-to-Practice (R-to-P) Model in 2002 to translate scientific evidence into program practice. Objectives: To describe the DHAP’s R-to-P Model. Methods: The R-to-P Model consists of three activities: Prevention Research Synthesis (PRS), Replicating Effective Programs (REP) and Diffusion of Effective Behavioral Interventions (DEBI). PRS conducts on-going systematic reviews to identify evidence-based interventions based on rigorous efficacy criteria that assess quality of study design, implementation, analysis, and strength of evidence. REP works with researchers and community-based partners to translate evidence-based interventions into user-friendly packages for agencies. DEBI coordinates the dissemination of packaged interventions by providing training, technical assistance, and other capacity building through the national network of STD/HIV Prevention Training Centers and capacity building assistance providers. Results: PRS has reviewed over 500 U.S.-based behavioral interventions for reducing HIV risk. Sixty-nine evidence-based interventions (EBIs) published through June 2009 were identified. Twenty-one REP packages have been completed. DEBI is currently disseminating 23 interventions (REP and other packages) to community-based organizations, health departments, and medical clinics. Conclusions: The DHAP’s R-to-P Model covers three important steps to translate scientific evidence from the research literature into practical materials that can be used in affected communities: research synthesis, technical translation, and large-scale dissemination with training and technical support. This model may be adopted by other fields that consider scaling up evidence-based prevention practices.