Suicide is the fourth leading cause of death among adolescents, globally. Though post-primary, school-based suicide prevention (PSSP) has the potential to be a key strategy for preventing adolescent suicidal thoughts and behaviours (STBs), there are persisting challenges to translating PSSP research to practice. Intervention and contextual factors relevant to PSSP are likely key to both PSSP effectiveness and implementation. As such, this systematic review aimed to summarise the effectiveness of PSSP for adolescent STBs and highlight important intervention and contextual factors with respect to PSSP. PsycINFO, Medline, Education Source, ERIC, Web of Science, and the Cochrane Central Register of Controlled Trials were searched to identify randomised and non-randomised studies evaluating the effectiveness of interventions located in post-primary, school-based settings targeting adolescent STBs. PSSP effectiveness and intervention and contextual factors were synthesised narratively. Twenty-eight studies were retained, containing nearly 47,000 participants. Twelve out of twenty-nine trials comparing intervention and independent control comparators reported statistically significant reductions in STBs postintervention, and 5/7 trials comparing preintervention and postintervention scores demonstrated significant reductions in STBs over time. Reporting and analysis of intervention and contextual factors were lacking across studies, but PSSP effectiveness and intervention acceptability varied across type of school. Although school personnel commonly delivered PSSP interventions, their input and perspectives on PSSP interventions were lacking. Notably, adolescents had little involvement in designing, inputting on, delivering and sharing their perspectives on PSSP interventions. Twenty out of twenty-eight studies were rated as moderate/high risk of bias, with non-randomised trials demonstrating greater risks of bias and trial effectiveness, in comparison to cluster randomised trials. Future research should prioritise complete reporting and analysis of intervention and contextual factors with respect to PSSP, involving key stakeholders (including adolescents and school personnel) in PSSP, and investigating key stakeholders' perspectives on PSSP. Given the inverse associations between both study quality and study design with PSSP effectiveness, particular consideration to study quality and design in PSSP research is needed. Future practice should consider PSSP interventions with universal components and PSSP which supports and involves key stakeholders in engaging with PSSP.