Background <p>Schools are key settings for youth suicide prevention, with current interventions typically targeting specific risk groups. However, integrating complementary prevention strategies may better address the heterogeneity of suicide risk in schools. This study evaluated the Multimodal Approach to Preventing Suicide in Schools (MAPSS), which combined universal suicide prevention training (safeTALK), selective screening for suicidal ideation, and an indicated online cognitive behavioural therapy intervention (Reframe-IT).</p> Methods <p>MAPSS was implemented across 21 secondary schools in Melbourne, Australia. The universal (safeTALK) and selective (screening) program elements were evaluated using a single-arm pre–post design (<i>n</i> = 1966) with outcomes including suicide literacy, stigma, and intentions to intervene. The indicated intervention (Reframe-IT) was evaluated in a parallel-group superiority randomised controlled trial (<i>n</i> = 93). Students reporting past-month suicidal ideation during screening and who consented to the trial were randomised to Reframe-IT plus treatment as usual (TAU; school-determined supports and external referrals) or TAU alone, with outcomes including suicidal ideation (primary), depression, hopelessness, and problem solving. Help-seeking, acceptability, and iatrogenic effects were assessed across the full program. Participants completed 4 assessments (T1: Baseline; T2: 2 weeks; T3: 12 weeks; T4: 24 weeks) with RCT outcomes assessed T2-T4.</p> Results <p>safeTALK was associated with modest improvements in intentions to intervene, suicide literacy, and perceived control, but not stigma. Screening identified 733 (37%) students experiencing suicidal ideation. In the RCT, suicidal ideation declined in both groups, with no greater reduction for Reframe-IT (<i>p</i> = .144; d = 0.31). Help-seeking increased during MAPSS, returning to baseline by 24-week follow-up. MAPSS was well tolerated with low distress, though some iatrogenic effects were observed.</p> Conclusions <p>MAPSS demonstrated feasibility and safety for delivering multimodal suicide prevention strategies in schools. The universal and selective components were associated with improved knowledge and skills to intervene and enabled identification of students reporting suicidal ideation. However, the indicated intervention conferred no added benefit, likely reflecting an underpowered trial, contextual barriers to delivery, and possible differences in TAU between groups.</p> Trial registration <p>Universal and Selective interventions ID: ACTRN12621000770864, originally registered on 21/06/2021, updated on 16/02/2025; Indicated intervention ID: ACTRN12621000279820, originally registered on 12/03/2021, updated on 13/04/2025.</p>