The Center for Substance Abuse Prevention (CSAP) is the federal agency charged with preventing and reducing substance use and related problems. CSAP's current prevention initiative, Partnerships for Success (SPF-PFS) is designed to address two of the nation's top substance abuse prevention priorities: 1) underage drinking among persons aged 12 to 20; and 2) prescription drug misuse and abuse among persons aged 12 to 25. CSAP recently funded a national cross-site evaluation to assess the effectiveness of funded grantees (N=31) to select and implement evidence-based interventions that address the targeted priority issues. This presentation will describe and highlight a comprehensive and innovative evaluation approach that was designed to address challenges associated with conducting similar efforts. Specifically, the presentation will include 1) an overview of the evaluation design, 2) a description of innovative approaches to prevent and reduce underage drinking and prescription drug misuse and abuse, and 3) preliminary findings to date.#2014Conference