| Summary: | Abstract Background The use of substances is a growing concern in Ethiopia, and their impacts on younger generation have been a concern of different professionals. Even though students are at high-risk of substance abuse, there is lack of comprehensive evidence for policy decision on substance use among students. Therefore, the aim of this systematic review and meta-analysis was to estimate the prevalence of common substances among students in Ethiopia. Method A comprehensive literature searches were done from biomedical databases: PubMed/Medline, African Journal Online, HINARI, Science Direct, and Google Scholar for article published until Dcember 31, 2017, and Addis Ababa Uiversity’s electronic library search of unpublished thesis and dissertations. Two authors autonomously selected studies, extracted data, and evaluated quality of studies. The prevalence of lifetime substances use was estimated using the random effects model. Q and I 2 statistics were computed to measure the extents of heterogeneity. Results A total 676 study articles were identified from electronic databases, and 28 of them were included in meta-analysis. The analysis revealed that the lifetime prevalence of any substance use was 52.5% (95% CI 42.4–62.4%), khat 24.7% (95% CI 21.8–27.7%), alcohol 46.2% (95% CI 40.3–52.2%), and smoking cigarette 14.7% (95% CI 11.3–18.5%). Significant heterogeneity was observed but there was no significant publication bias. The lifetime prevalence of khat, alcohol, and cigarette smoking among high school vs university students was 22.5% (95% CI 15.2–30.7%) vs 25.1% (95% CI 21.9–28.5%), 41.4% (95% CI 22.1–62.1%) vs 47.8% (95% CI 39.9–55.7%), and 21.5% (95% CI 12.6–32.1%) vs 12.9% (95% CI 10.1–16.0%), respectively. Conclusion This meta-analysis highlighted the extent of lifetime prevalence of any substance, khat, alcohol, and cigarettes smoking among students in Ethiopia. Significant percent of high school students have exposed to substances. Policy makers should devise and implement strictly binding regulation to curb widespread of substances around educational institution premises at national level. Priority should be given to intervention strategies that help delay first use of substance to prevent problems later in life. Besides, the problem warrants regular national-level educational institutions based studies focusing on the magnitude, trajectory, and consequences of substance use among students. Systematic review registration: PROSPERO CRD42018082635
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