ABSTRACT More than 75% of suicide deaths occur in low-and middle-income countries (LMICs) and almost 90% of adolescents who die by suicide live in LMICs. Globally, suicide is the fourth leading cause of death for youth aged 15-29. Six of the top 10 countries by suicide rates in the world are in the African region. Despite this, there are few to no evidence-based youth suicide prevention packages specifically developed for, and tested in, the African context. This is an urgent need to safeguard the well-being of youth and young adults globally. Data from our team suggest that 15-25% of high school students in Mozambique are experiencing current suicidal ideation, ~40% of those with ideation have past month suicidal behavior, and 9% have had a lifetime suicide attempt. To address this problem, we aim to test effectiveness and implementation outcomes for a novel suicide prevention package organized around the Suicide Safety Planning Intervention (SPI) and a Transdiagnostic Cognitive Behavioral Therapy Intervention for Suicide Prevention (TCBT-S) to be delivered by non-specialists in Mozambican secondary schools. We believe that these two evidence-based practices, both with demonstrated feasibility in Mozambique, have the potential to be powerful interventions to prevent adolescent suicidal behavior. Yet, a recent meta-analysis found lower comorbidity of psychiatric disorders and suicidal behavior in LMICs (~50%) compared to high-income countries (~90%). Therefore, it is possible that applying TCBT-S to address psychiatric symptoms may not lead to significant decreases in suicidal behavior above and beyond SPI alone. Therefore, we aim to evaluate whether the gains in effectiveness for youth suicide prevention justify the addition of a much more resource intensive TCBT-S versus the brief SPI alone. The present study aims to fill this knowledge gap by testing the following specific aims: Specific Aim 1: Test the effectiveness of SPI and TCBT-S for decreasing suicidal behaviors. Using a three- arm parallel cluster randomized trial we will randomize 7 secondary schools each to Enhanced Usual Care (EUC), SPI alone, and TCBT-S (21 schools total) to evaluate effects on suicidal behaviors (primary) and suicidal ideation/depressive symptoms (secondary). Exploratory analyses will examine mechanisms of intervention effects. Specific Aim 2: Assess implementation outcomes, barriers, and facilitators to EUC, SPI, and TCBT-S implementation using the RE-AIM evaluation and CFIR determinant frameworks. Specific Aim 3: Estimate the costs and cost-effectiveness of SPI and TCBT-S compared to EUC. In response to the NOSI for Youth Suicide in LMICs (NOT-MH-21-090), this project proposes to test “prevention strategies to reduce suicide risk and promote resilience among young people aged 10-24 years in LMICs”. Specifically, this study “integrates suicide prevention strategies within existing community-level platforms such as school/university-based programs”. If effective, SPI or TCBT-S have a large potential to be rapidly scaled up for youth mental health globally.