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Background: Since there is currently no conclusion on the efficacy and adverse effects of oxymetazoline, this meta‐analysis attempts to explore its efficacy and adverse events, so as to provide guidance for clinical medication. Methods: We searched PubMed, Embase, and Cochrane Library from the establishment of the database to May 2021. We included studies that patients were randomly assigned to receive oxymetazoline or vehicle, and we excluded duplicate publications, research without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. Results: The pooled results show that the 3 (RR = 1.76, 95% CI: 1.53–2.03), 6 (RR = 1.71, 95% CI: 1.47–2.00), 9 (RR = 1.63, 95% CI: 1.40–1.90), 12 (RR = 1.41, 95% CI: 1.18–1.67) ‐hours CEA success rate and the 3 (RR = 1.65, 95% CI: 1.34–2.03), 6 (RR = 1.75, 95% CI: 1.43–2.14), 9 (RR = 1.63, 95% CI: 1.33–2.00), 12 (RR = 1.78, 95% CI: 1.45–2.18) ‐hours SSA success rate after oxymetazoline treatment for rosacea is significantly higher than that of vehicle. Additionally, the pooled results show that the incidence of TEAEs after treatment with oxymetazoline is significantly higher than that of vehicle (RR = 1.34, 95% CI: 1.10–1.2). However, our analysis of specific adverse events found that the oxymetazoline group was only significantly higher than the vehicle group in the incidence of application‐site dermatitis (RR = 8.91, 95% CI: 1.76–45.23), and there was no statistical significance in the difference in the incidence of other adverse events. Conclusion: Oxymetazoline is effective and can be selected for the treatment of persistent facial erythema of rosacea. Additionally, application‐site dermatitis was the most important one. [ABSTRACT FROM AUTHOR]