PROJECT SUMMARY/ABSTRACT To build the evidence base for innovative school-based or school-linked strategies aligned with the Centers for Disease Control and Prevention’s (CDC’s) What Works in Schools (WWIS) approach to promote the health of American Indian/Alaska Native (AI/AN) youth, it is imperative to implement and evaluate culturally tailored programming that addresses AI/AN youth’s unique health needs while preserving their Indigenous identity. To address this need, the San Juan School District (SJSD) Wellness Demonstration Project seeks to align the SJSD’s current school-based wellness programing to CDC’s WWIS approach, conduct a mixed-methods applied evaluation of the SJSD Wellness Program, and pilot an adapted professional development intervention for health education teachers. To accomplish our goal, we propose the following specific aims: (1) to conduct a formative assessment of the SJSD’s current school-based and school-linked Wellness Program strategies; (2) to conduct a process evaluation of the SJSD Wellness Program to assess facilitators and barriers to program implementation, determine the acceptability of CDC’s WWIS approaches, and replicate and scale strategies to broader populations; (3) to conduct an outcome evaluation of the SJSD Wellness Program to examine primary and secondary outcomes of WWIS-aligned approaches being implemented by the SJSD, including associated student-level outcomes, such as sexual and reproductive health behaviors, mental health and suicide-related behaviors, substance use, and experiences of violence among AI/AN students, and environmental-level outcomes such as parent and community engagement and safe and supportive school environments; and (4) to identify, culturally adapt, and pilot a WWIS-aligned professional development (PD) program for middle school and high school health teachers and assess teacher-level outcomes (e.g., instructional competency). The SJSD Wellness Demonstration Project will use community-based participatory research approaches appropriate for Indigenous evaluation including listening sessions, individual key informant interviews, and observations. In addition, a combination of quasi-experimental methods will be used to explore relationships between SJSD’s WWIS-aligned school-based strategies and priority outcomes. Two frameworks, the Indigenous Evaluation Framework and the Knowledge to Action Framework for Public Health, will anchor all evaluation components and translation/dissemination efforts.