Purpose: In dialysis patients, painful peripheral neuropathy (PPN) is associated with sleep disturbance and mood disorders. Our goal was to compare the effects of gabapentin and pregabalin on improving sleep quality and depression among hemodialysis patients with PPN. Methods: Fifty hemodialysis patients with PPN were randomized into 2 groups, to receive gabapentin and pregabalin, respectively. After 6 weeks of treatment, patients underwent a 2-week washout period, followed by crossover and another 6 weeks of treatment. All patients underwent electromyography (EMG) at the outset and completed the modified Short Form of McGill Pain Questionnaire (SF-MPQ), the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality (PSQI) assessment at baseline and at the end of the study. Forty out of 50 patients completed the 14-week study period. Results: Thirty-one out of 40 patients (77.5 %) had EMG-proven PPN. Both gabapentin and pregabalin significantly improved SF-MPQ, BDI and PSQI scores at the end of the study compared with pretreatment scores (p < 0.001). There was no significant difference between the two drugs in any studied parameter. ConclusIons: Our results showed for the first time a good and similar efficacy of both drugs on pain intensity, quality of sleep and depression in hemodialysis patients with PPN. © 2012 Springer Science+Business Media, B.V.