Communities That Care (CTC) is a prevention system designed to reduce adolescent substance use and delinquency through the selection of effective preventive interventions tailored to a community's specific profile of risk and protection. A community-randomized trial of CTC, the Community Youth Development Study, is currently being conducted in 24 communities across the United States. This article describes the rationale, multilevel analyses, and baseline comparability for the study's longitudinal cohort design. The cohort sample consists of 4,407 fifth- and sixth-grade students recruited in 2004 and 2005 and surveyed annually through ninth grade. Results of mixed-model ANOVAs indicated that students in CTC and control communities exhibited no significant differences (ps > .05) in baseline levels of student outcomes.