Reducing youth suicide in the U.S. is a national public health priority. A supportive and safe school environment is pivotal to preventing youth suicide, and schools are now widely accepted as part of the de facto mental healthcare infrastructure for adolescents. Lesbian, gay, bisexual, transgender, and intersex (LGBTI) youth are at elevated risk for suicide. Safer school environments decrease this risk. The school nurse is well positioned to implement evidence-based (EB) strategies to enhance school environments and improve the mental health of all students, particularly members of this vulnerable population. These strategies include the creation of safe spaces, adoption of harassment and bullying prohibitions, improved access to community health and mental health providers experienced in working with youth and LGBTI people, school staff development, and incorporation of LGBTI-specific information into health education curricula. These strategies promote positive mental health outcomes for LGBTI youth, and their cisgender, heterosexual peers as well. Our nursing intervention model is called RLAS (Implementing School Nursing Strategies to Reduce LGBTI Adolescent Suicide). It builds on the Exploration, Preparation, Implementation, and Sustainment conceptual framework and the Dynamic Adaptation Process (DAP), a structured methodology for implementing the EB strategies. The DAP accounts for the multi-level context of school settings, facilitates appropriate expertise and feedback to make them implementation ready, and provides for targeted training of school nurses. Per the DAP, the nurses will convene and lead Implementation Resource Teams (IRTs) consisting of counselors, social workers, health educators, and youth. With the guidance of coaches, the IRTs will engage in an iterative process of assessment and planning to build school capacity and implement the EB strategies. To evaluate this model, we combine qualitative methods with population-based surveys and pursue three specific aims. First, we will utilize the DAP to enable specially-trained nurse champions and IRTs to implement and sustain EB strategies to address the needs of LGBTI high school students. Second, we will conduct a cluster randomized controlled trial (RCT) to assess whether sexual minority students and their peers in RLAS schools report reductions in suicidality, depression, substance use, and bullying, and increased safety compared to those in usual care schools. Third, we will examine the individual, school, and community factors influencing both implementation and outcomes. The RLAS keeps with national priorities to: (a) improve school-based services for pediatric populations; (b) focus on LGBTI youth mental health; and (c) revolutionize the role of nurses in U.S. healthcare. Through its collaborative processes to refine, improve, and sustain EB strategies in these systems, the RLAS also represents a novel and innovative contribution to implementation science.