Background and Rationale: Asthma, the most common pediatric chronic illness, has high prevalence and morbidity among adolescents. Few interventions are tested in high schools; none when delivered by Community Health Workers (CHWs), despite this model's success in clinic- and home-based interventions. Further, rural adolescents, who represent a very large population, are overlooked in asthma intervention research. Given the high prevalence of asthma in this group, this oversight is a significant public health concern. Cost effectiveness analyses and implementation research are also lacking in asthma intervention research. This study addresses these treatment and methodological gaps. We developed and established the efficacy of Asthma Self-Management for Adolescents (ASMA), an 8-week, high school-based intervention, in urban Hispanic and African American adolescents. Objective: Using an effectiveness-implementation hybrid design, we: (1) evaluate systematically the effectiveness of ASMA when delivered under real world conditions by CHWs to rural adolescents with uncontrolled asthma; (2) assess the cost-effectiveness of ASMA; and (3) conduct a theory-based, mixed-methods, multi-stakeholder process evaluation of the barriers and facilitators of ASMA's widespread implementation. Hypotheses: Over 1 year, relative to controls, ASMA students will have significantly fewer (1) night awakenings due to asthma symptoms, and (2) days with asthma-related activity limitations (primary outcomes). Secondary outcomes include other measures of morbidity (e.g., ED visits, hospitalizations, quality of life) and care-process outcomes. We also hypothesize that ASMA will have favorable value (ICER < 100,000/QALY) compared to alternative uses of health care resources over 1 and 5 years. Methods: We will enroll over 3 years, 400 9th through 11th grade students with uncontrolled asthma from 9 high schools in rural communities in South Carolina; we will randomize students within a school to ASMA and to an attention control condition. CHWs will deliver both interventions. Students and caregivers will be followed for 12-months post-treatment. The intention-to-treat (ITT) principle will be applied using linear and general linear mixed effects models. The cost-effective analysis will rely on a decision-analytic Markov model. The process evaluation is built on the RE-AIM model; we collect qualitative and quantitative data from students, caregivers, CHWs and school administrators. Together with key stakeholders from a variety of settings, we will develop models to widely disseminate and implement ASMA. Significance: The study has high public health significance because (1) it targets an understudied population, (2) it relies on existing community resources for intervention implementation, (3) it assesses ASMA's value through cost-effectiveness analyses, and (4) it bridges the gap between research and practice by identifying factors associated with implementation.