Introduction: Restless leg syndrome (RLS) is a sensory motor disorder. Patients with this syndrome have serious and uncontrollable desire to move their legs, which is mostly due to an uncomfortable feeling intensified when they are motionless. It may be a genetic disorder or secondary to iron deficiency, neurodegenerations, pregnancy, some drugs and severe kidney diseases. Objectives: This study was designed to find out the prevalence and its risk factors of RLS in hemodialysis patients. Patients and Methods: This multicenter cross-sectional study was done on 260 hemodialysis patients. The prevalence of RLS was measured using International Restless Legs Syndrome Study Group (IRLSSG)’s RLS Questionnaire (RLSQ). Potential risk factors for RLS including underlying cause of chronic renal failure, duration on dialysis, biochemical tests, dialysis adequacy, and erythropoietin and also venofer dosage in recent month and demographic data were also evaluated. Results: The prevalence of RLS was 55% including 59.4% males and 40.6% females. Their mean age of RLS patients and their dialysis duration were significantly higher than other group (P<0.05). Their body mass index (BMI) and serum calcium were significantly higher (P<0.05). However erythropoietin dosage and serum hemoglobin level were lower in RLS patients (P<0.05). Significant predictors of RLS were history of diabetes mellitus (DM), hypertension (HTN), smoking (P<0.05). There was not significant relation between RLS and dialysis adequacy, serum intact parathyroid hormone (iPTH), urea, ferritin and venofer dosage (P>0.05). Conclusion: According to the results, RLS is a common disorder in hemodialysis patients which can affect strongly on their life. So particular attention and sooner diagnosis of RLS in high risk patients for better management is necessary.