BACKGROUND Alcohol use impairs psychosocial and neurocognitive development and increases youth vulnerability to academic failure, substance use disorder and other mental health problems. Early adolescent alcohol use onset is of particular concern, forecasting substance abuse in later adolescence and adulthood. Evidence to date suggests that youth in rural areas are especially vulnerable to contextual and community factors that contribute to early onset of alcohol use. OBJECTIVE The objective of the Young Mountaineer Health Study (YMHS) is to investigate the influence of contextual and health behavior variables on early onset of alcohol use among middle school-aged youth in resource-poor Appalachian rural communities. METHODS This is a program of prospective cohort studies of ~2,200 middle school youth from a range of twenty rural, small town, and small city (< 30k) public schools in West Virginia. Students participate in 6 waves of data collection (2 per year), over the course of middle school (6th- 8th grades, fall and spring). Based on an organizational arrangement which includes a team of local data collection leaders, supervising contact agents in schools, and an “honest broker” system to de-identify data linked via school IDs, we have been able to collect novel forms of data (self-report, teacher-report, census linked area data, and archival school records) while ensuring high rates of participation by a large majority of youth in each participating school. RESULTS To date, three waves of student survey data, two waves of teacher data, and a selection of archival school records have been collected. Student survey Wave 1: N = 1,349 (response rate = 80.7%), Wave 2: N = 1,649 (response rate = 87.0%), and Wave 3: N = 1,909 (response rate = 83.1%). The COVID-19 pandemic had a negative impact on the sampling frame size, resulting in a reduced number of eligible students, particularly during the fall of 2020. Nevertheless, our team structure and incentive system has proven vitally important in mitigating a potentially far greater negative impact of the pandemic on our data collection processes. CONCLUSIONS The YMHS will employ a large dataset to test pathways linking rural community disadvantage to alcohol misuse among early adolescents. Further, the program will test hypotheses regarding contextual factors (e.g., parenting practices, neighborhood collective efficacy) that protect youth from community disadvantage, and explore alcohol antecedents in the onset of nicotine, marijuana, and other drug use. So far, data collection efforts have been successful despite interruptions caused by the COVID-19 pandemic. Data quality checking, preliminary analyses, and manuscript preparations are currently under way. CLINICALTRIAL N/A