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Purpose: Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via 5HT3 receptor antagonism., Design: Systematic review and meta-analysis., Methods: We identified seven randomized controlled trials by systematically searching electronic databases that compare the efficacy of mirtazapine versus placebo or ondansetron in reducing PONV., Findings: Mirtazapine reduced PONV overall versus placebo in three studies (risk ratio [RR] = 0.44; 95% confidence interval [CI] 0.32 to 0.62) both on conventional meta-analysis and trial sequential analysis. One study comparing mirtazapine with ondansetron found similar rates of PONV (RR = 0.96; 95% CI 0.48 to 1.94). Mirtazapine reduced preoperative anxiety versus placebo or ondansetron (standardized mean difference -1.4; 95% CI -2.56 to -0.23) but increased sedation (RR = 22.47; 95% CI 5.61 to 89.93). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality of evidence was moderate to low., Conclusions: This meta-analysis suggests that mirtazapine reduces PONV overall versus placebo. We found evidence of reduction in preoperative anxiety, although mirtazapine increased the risk of sedation., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)