ABSTRACT Social experiments provide valuable insight into the effectiveness of real-world policies and programs. Previous experiments have demonstrated that education interventions substantially improve health and other life outcomes, such as incarceration and pregnancy, but only when intervention occurs during early childhood. However, recent research suggests there may be a dose-response effect. Thus, education interventions among adolescents may improve health, but requires longer-term follow up. We propose a renewal of our NIDA-funded R01, the RISE UP Study, which used the admission lottery of high-performing public charter high schools to study comparable cohorts of students exposed to high- and low- performing schools. In 2013 and 2014, we recruited 1270 adolescents who had applied to one or more high performing charter schools in low-income neighborhoods of Los Angeles. Subjects completed baseline surveys in 8th grade after the high school admission lottery, and then annual surveys through 11th grade. Lottery ?winners? and ?losers? are comparable in study retention rates (87% at 3 years), demographics, grade point average in 8th grade, and baseline marijuana and alcohol use. After 3 years, lottery winners have substantial improvement in intermediate school outcomes (lower rates of truancy and switching schools, which is a risk factor for dropping out) better school experiences (more supportive teachers, less chaotic school environments, more positive behavioral culture), and lower rates of substance use (risky marijuana use, 30- day marijuana use, and risky alcohol use). Most of these differences were much larger or only occurred among boys. The transition to adulthood is an important developmental period during which many individuals are completing their education and making life choices about career, family, marriage, and substance use that will have a profound impact on their future health and socioeconomic trajectory. We hypothesize that better high school education will affect health behaviors and outcomes during this transition time as a result of higher educational attainment, improvement in employment, and changes in social networks and neighborhoods after high school. Thus, the study aims are to follow the RISE UP cohort through age 21 and examine the impact of exposure to a high performing school on substance use, pregnancy, depression, obesity and other life events including employment, college matriculation and criminal arrests. We will examine heterogeneity of the intervention effects by gender and length of exposure to rigorous school environments (including college). We will also conduct exploratory analyses to determine if social networks and social-emotional factors (self-efficacy, grit, hopelessness, and depression) mediate the effect of education on health. Findings from this research have implications for how educational policies might be shaped to improve health, and specifically whether improving public high schools can help reverse the negative health effects of poverty.