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ObjectiveThis systematic review examined the effectiveness of Emergency Department-based and initiated youth suicide prevention interventions for suicide attempts, suicidal ideation, hospitalization, family system functioning, and other mental health symptoms.MethodsWe searched five databases for randomized controlled trial (RCT) studies that examined Emergency Department-based and initiated suicide prevention interventions among youth aged 10 to 18 years old between May 2020 to June 2022. Using Cohen’s d and 95% confidence interval as our standardised metrics, we followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) and Synthesis Without Meta-Analysis in Systematic Reviews (SWiM) guidelines when synthesizing, interpreting, and reporting the findings of this review.ResultsFive studies were included in this review. Findings were first synthesized according to the targeted population of the study intervention and this review’s outcomes. Two interventions were effective for decreasing depressive symptoms, hospitalization recidivism, and/or increasing family empowerment. There were no interventions that reduced subsequent suicide attempts. A meta-analysis was not conducted due to the heterogeneity of the data.ConclusionA need exists to develop and evaluate Emergency Department-based and initiated youth suicide prevention interventions that can be successfully and sustainably implemented in practice. Future research should focus on evaluating the components of interventions that effectively mitigate suicide risk among high-risk youth.