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Trichomonas vaginalis is the most common curable sexually transmitted infection worldwide. Although the Centers for Disease Control and Prevention and the World Health Organization recommend a single 2-g dose of metronidazole for the first line of treatment for T. vaginalis among human immunodeficiency virus (HIV) negative women, high rates of repeat infections are found. The purpose of this meta-analysis was to compare treatment failure between single versus multidose metronidazole for the treatment of T. vaginalis.A systematic literature search was performed using search terms including metronidazole AND trichomoniasis AND women. Embase, MEDLINE, and Clinicaltrials.gov were used to search for relevant studies as well as hand searching relevant articles. These databases were last searched on January 25, 2016. To be included in this meta-analysis, the study had to be a clinical trial, evaluate T. vaginalis, use oral metronidazole, and compare single dose metronidazole to multidose metronidazole.There were 487 articles that were assessed for relevance and quality. Of these articles, 6 met the eligibility criteria and were included in the final results. The pooled risk ratio indicated higher treatment failure for single dose compared to multidose 1.87 (95% confidence interval, 1.23–2.82; P < 0.01). When the one study that included HIV+ women was excluded from analysis, the findings were similar with a pooled risk ratio of 1.80 (95% confidence interval, 1.07–3.02; P < 0.03).Centers for Disease Control and Prevention recently changed treatment recommendations for HIV+ women to multidose rather than single-dose. These data suggest that those recommendations should be considered for all women.