Objectives -To determine clinical and laboratory predictors of restless legs syndrome (RLS) in patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis (HD). Materials and methods One hundred and sixty-two consecutive patients were assessed. History of sleep disturbances, neurological examination, clinical, and laboratory data were collected. Patients with and without RLS were compared, and a logistic regression model described the relations between independent predictors and RLS. Results -Fifty-one patients (32%) currently had RLS (RLS+). RLS+ vs RLS) patients were more frequently women (49% vs 29%, P = 0.012), had first-degree relative with RLS (22% vs 6%, P = 0.004), insomnia (59% vs 36%, P = 0.007), peripheral neuropathy (41% vs 21%, P = 0.006), and low residual diuresis (92% vs 68% with below 500 ml / 24 h, P = 0.001). Low (OR = 8.71, CI = 2.27-33.41; P = 0.002) and absent (OR = 4.96, CI = 1.52-16.20; P = 0.008) residual diuresis, peripheral neuropathy (OR = 4.00, CI = 1.44-11.14; P = 0.008), and first-degree relative with RLS (OR = 3.82, CI = 1.21-12.13; P = 0.023) significantly predicted RLS in ESKD patients undergoing HD. Conclusions -Positive family history for RLS together with reduced / absent residual renal function and peripheral neuropathy predicts the risk for RLS in ESKD patients undergoing HD. Longitudinal studies are warranted to correlate RLS occurrence with genetic and environmental factors.