Background: Restless legs syndrome (RLS) is a common disorder in hemodialysis (HD) patients that causes sleep disturbances and diminished quality of life. Because iron deficiency has been implicated in the pathogenesis of RLS, we sought to investigate the effects of intravenous (IV) iron sucrose on symptoms of RLS in HD patients. Material/Methods: The study was a randomized, placebo-controlled study of 1000 mg iron sucrose versus normal saline as placebo. Patients were evaluated at baseline and 2 weeks after the last injection. The severity of RLS was assessed using the International RLS Study Group rating scale (IRLS). Blood samples were taken to measure iron parameters reflecting the iron status, including serum ferritin (SF) concentration, percentage transferrin saturation (TSAT%) and hemoglobin (Hb), and other biochemical parameters as safety assessments, including creatinine (Cr), urea, intact parathyroid hormone (iPTH), and the index of urea clearance (Kt/V). Adverse events were monitored in all subjects during the period of infusion. Results: After 2 weeks, IRLS scores decreased more in the IV-iron group (-7.38 +/- 2.03) than in the placebo group (-0.81 +/- 2.61) (P=0.000). Serum ferritin, TSAT, and hemoglobin increased more in the IV-iron group (227.63 +/- 77.64 mu g/L; 26.06 +/- 7.77%; 13.98 +/- 3.62g/L, respectively) than in the placebo group (SF, p= 0.000; TSAT, p= 0.000; Hb, p= 0.000, respectively). There were no significant differences between IV-iron and placebo groups in Cr, urea, iPTH, and Kt/V. No adverse effects were observed in the study. Conclusions: IV iron sucrose is a safe and effective treatment for reducing RLS symptoms in HD patients over the short-term.