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Background: Post-stroke depression is common and it impedes rehabilitation and function recovery after stroke, and numerous trials evaluated SSRI’s for depression prophylaxis. The objective of this study is to assess the use of SSRI for prevention of poststroke depression and the potential effect on functional recovery after stroke. Methods: We searched electronic databases up to July 2019 for randomized controlled trials of SSRI’s for patients with stroke versus placebo. We calculated pooled odds ratios and 95% CIs by using random-effects models. The primary end points were depression and good functional outcome (modified Rankin Scale score of 0-2) at 90 days post-randomization. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Twelve randomized control trials assessing 4,887 patients have been included in the meta-analysis. SSRI treatment after stroke decreased the odds of depression compared to control group (OR = 0.48, 95% CI - 0.30 to 0.78, p=0.003). There was no heterogeneity between the trials (Cochran’s Q statistic 4.623, df 5; P = .337, I 2 =5.626%). The proportion of subjects who achieved mRS 0-2 at 90 days was similar between SSRI and control groups (OR= 3.471, 95% CI - 0.59 to 20.38, p=0.168). Conclusion: SSRI treatment for the stroke patients reduces the incidence of depression but it does not increase the odds of good functional recovery.