Restless legs syndrome (RLS) increases the risks of cardiovascular disease and death in hemodialysis (HD) patients. Previous studies of risk factors for RLS in HD patients have yielded varying results. We attempted to identify risk factors for RLS in HD patients in Taiwan.This case-control study recruited 59 HD patients with RLS and 353 HD patients without RLS from the largest HD center in Taiwan during the period from April 1, 2015 through August 31, 2015. Demographic and disease characteristics, information from the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic questionnaire, and IRLSSG Severity Scale scores were collected by interview. Clinical laboratory data were abstracted from medical records and then analyzed with logistic regression and Pearson correlation analysis. A P value of less than .05 was considered to indicate statistical significance.A dialysis duration of longer than 5 years (odds ratio [OR] = 2.32; 95% CI = 1.23-4.39; P = .002) and a low high-density lipoprotein cholesterol level (<40 mg/dL in men; <50 mg/dL in women) (OR = 2.73; 95% CI = 1.44-5.15; P = .009) were associated with increased risk of RLS. Among the 59 patients with RLS, 48 (81.3%) had moderate or severe symptoms (IRLSSG Severity Scale >10), and RLS severity was significantly correlated with dialysis duration (r = .26; P = .043).Among HD patients, RLS was more common among those receiving dialysis for longer than 5 years and those with a low serum high-density lipoprotein cholesterol (HDL-C) level.