This article describes, compares, and contrasts the contexts, processes, and results of the experiences of Maryland and Massachusetts in diffusing evidence-based interventions. The evolution of first Maryland's, then Massachusetts's, diffusion of effective interventions is described. Both states have extensive experience planning, developing and evaluating individual-, group-, and community-level interventions promoted in the Centers for Disease Control and Prevention's Diffusion of Effective Behavioral Interventions (DEBI) initiative, as well as overcoming many barriers to translate research to practice. This article describes the processes whereby effective interventions were diffused from the planning to evaluation stages. This includes the role of community-planning groups and other local stakeholders in planning, procurement methods, and capacity building approaches. Specific milestones in increasing the evidence basis of program implementation, management, and evaluation are presented. For jurisdictions considering implementing DEBI, the article illustrates core programmatic and infrastructure capacities at the state and vendor level important to success in Maryland and Massachusetts. It also describes how each state's approach to the management and evaluation of prevention programs contributed to the effective diffusion of the behavioral interventions. Finally, this article provides recommendations about remaining gaps in evidence-based interventions to meet "real-world prevention needs" and ways to improve prevention targeting and effectiveness. This article recommends strategies to improve the dissemination of DEBI and other evidence-based interventions nationally.