Innovative analysis of existing social science and behavioral data has the potential to advance our understanding of the epidemiology and etiology of marijuana and other substance use among adolescents and emerging adults, so as to inform future policy, prevention, and intervention efforts. In this commentary, we highlight two commonly used and publicly available datasets, the National Survey on Drug Use and Health (NSDUH) and the Youth Risk Behavioral Survey (YRBS), in order to describe their usefulness for evaluation of the effects of changes in marijuana policy on adolescent and emerging adult substance use and marijuana-specific risk factors. We use recent examples of trend and quasi-experimental studies to highlight the unique strengths of each dataset. We also describe their limitations, identify gaps in existing knowledge, and offer recommendations for future research to answer emergent questions about the changing legal, social, and normative context related to marijuana and contribute to prevention efforts aimed at reducing substance use and related health risk behaviors among youth.