ABSTRACT Education impacts health by improving access to socioeconomic resources and high-quality care (SES mechanism) and by improving literacy and numeracy, which aids in self-care and navigating the healthcare system (cognitive mechanism). But education does not just involve the acquisition of knowledge or cognitive skills. Education encompasses the experiences of being in a school environment, shaped by teachers, peers, and the “culture” of the school. Also referred to as school climate, these characteristics shape socioemotional factors that influence resilience and one's health trajectory (resilience mechanism). Almost all prior studies of education and health have relied on observational methods. In 2013, we began the Reducing Inequities through Social and Educational Change Follow-up (RISE Up) Study, a natural experiment using the admissions lottery of several high-performing public charter high schools to identify comparable groups of adolescents “randomized” into high- and lower-performing schools. We recruited students upon high school entrance and continue to follow this cohort currently (now age 22) with average annual retention rates of 96%. We found the impact of schools on self-reported health and health behaviors was immediate, substantial, and persistent beyond adolescence. By age 21, those who had attended a high-performing high school had a 50% lower rate of alcohol use disorder, 40% reduction in reporting fair or poor physical health, and 33% reduction in obesity/overweight. However, the improvements in physical health and obesity were only among males. Among females, attending a high-performing schools was associated with lower rates of alcohol use disorder, but substantially worse physical health and obesity. Surprisingly, intermediate academic outcomes (high school graduation, grade point average, test scores, and college matriculation) did not explain the impact of high-performing schools on substance use or physical health outcomes. Understanding how education influences health will inform the development of future interventions and school policies to make schools “healthier” for all students. Furthermore, our results to date are based on self-report. Thus, we proposed to follow the RISE Up cohort from age 23-28 to better understand how schools impact physiologic health perhaps through changes in socioemotional factors and resilience. We will measure blood pressure and body mass index and obtain blood samples to measure glycohemoglobin and C-reactive protein. We will examine epigenetic aging (DNA methylation), chronic stress (hair cortisol), and physiologic resilience using the Conserved Transcriptional Response to Adversity (CTRA). CTRA is a gene expression profile activated by fight-or-flight signaling from the sympathetic nervous system and related to greater inflammation and lower Type I interferon innate antiviral responses. Furthermore, we will explore sex differences in the relationship between education and physi...