Substance use has acute and chronic detrimental impacts on public health. However, risk for use is not conferred equally across the population, the life course, or birth cohorts. There are central unanswered questions about when and for whom risk factors are most important in contributing to substance use (tobacco, alcohol, marijuana, and other drug use) in young adulthood (YA), and the extent to which substance use in YA leads to adult health consequences, , including substance use disorders, sexual risk behavior, and physical/mental health. We will use national panel data from 38 high school senior year cohorts (1976 to 2013), with specific emphasis on 20 cohorts of individuals with longitudinal data across ages 18 to 35 (N~24,000) from Monitoring the Future (MTF) to examine significant unanswered questions regarding adolescent and YA substance use behaviors and adult health outcomes. Leading-edge statistical methods applied to MTF data will be used to model the dynamic associations between risk factors and risk behaviors across YA, and the extent to which these behaviors predict health consequences. Aim 1 will examine questions regarding variations in the epidemiology and etiology of substance use across age, cohort, social role statuses, and demographic subgroups. Aim 2 will examine the long-term consequences of YA substance use on the acquisition and timing of social role statuses and health into adulthood. Aim 3 will focus on disseminating new and advanced methodological techniques for examining risk factors, behaviors, and consequences. Results will advance our understanding of these behaviors so critical to health, and will inform the development of tailored interventions that take into account individual behaviors, characteristics, and roles in informing intervention strategies that may be most appropriate and effective for reducing the negative consequences of drug use in young adulthood.