Objective: Restless legs syndrome (RLS)is a common neurological disorder of unclear pathophysiology that appears to involve an iron deficiency in the brain. Some studies, but not others, suggest that intravenous injection of iron can reduce RLS severity. Method: The databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for randomized controlled trials, cohort studies and case-control studies of intravenous iron therapy to treat RLS. Eligible studies were meta-analyzed using Stata 12.0. Results: This analysis indicated that IV iron was more efficacious than placebo in treating RLS (OR: 4.71,95% CI 4.21-5.21, p < 0.0001). According to sub-group analysis, either IV ferric carboxymaltose (FCM) or iron sucrose was more efficacious than placebo in treating RLS. Adverse events did not differ significantly between patients receiving intravenous iron or placebo (OR 1.68, 95% CI 0.92-3.07, p = 0.093). The present study also indicated after accepting IV iron treatment the IRLS score in RLS patients decreased (OR = 6.75,95% CI 4.02-9.49, p < 0.0001). The subgroup analysis showed that IV iron dextran, iron sucrose, and FCM could alleviate the IRLS score. Conclusion: The available evidence suggests that intravenous iron is effective and tolerable for patients with RLS regardless of peripheral iron status. (C) 2019 Elsevier B.V. All rights reserved.