Suicide is one of the leading causes of death among young people globally. In light of emerging evidence supporting the effectiveness of school-based suicide prevention programmes, an analysis of cost-effectiveness is required. We aimed to conduct a full cost-effectiveness analysis (CEA) of the large pan-European school-based RCT, Saving and Empowering Young Lives in Europe (SEYLE). The health outcomes of interest were suicide attempt and severe suicidal ideation with suicide plans. Adopting a payer's perspective, three suicide prevention interventions were modelled with a Control over a 12-month time period. Incremental cost-effectiveness ratios (ICERs) indicate that the Youth Aware of Mental Health (YAM) programme has the lowest incremental cost per 1% point reduction in incident for both outcomes and per quality adjusted life year (QALY) gained versus the Control. The ICERs reported for YAM were 34.83 and 45.42 per 1% point reduction in incident suicide attempt and incident severe suicidal ideation, respectively, and a cost per QALY gained of 47,017 for suicide attempt and 48,216 for severe suicidal ideation. Cost-effectiveness acceptability curves were used to examine uncertainty in the QALY analysis, where cost-effectiveness probabilities were calculated using net monetary benefit analysis incorporating a two-stage bootstrapping technique. For suicide attempt, the probability that YAM was cost-effective at a willingness to pay of 47,000 was 39%. For severe suicidal ideation, the probability that YAM was cost-effective at a willingness to pay of 48,000 was 43%. This CEA supports YAM as the most cost-effective of the SEYLE interventions in preventing both a suicide attempt and severe suicidal ideation.Trial registration number DRKS00000214.