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Background: Cough is the most common presenting symptom for consulting in primary care. Oxomemazine is the second most reimbursed medication in France, among those approved for the symptomatic treatment of coughs. Objective: The aim of this study was to assess the efficacy of oxomemazine in treating cough. Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs), according to the Rebuild the Evidence Base (REB) protocol. We included clinical trials comparing oxomemazine with a placebo or active controls in treating cough. We searched the following databases and registries to identify studies: Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov. Results: None of the RCTs had a low risk of bias. In accordance with the REB protocol, no meta-analysis was carried out. Conclusion: This systematic review of the literature concludes that oxomemazine has not been adequately assessed in the treatment of cough and that there is no evidence of clinical efficacy according to the REB method.