Background: Painful peripheral neuropathy (PPN) is common in haemodialysis patients and associated with impaired health-related quality of life (HR-QoL). Gabapentin and pregabalin have not been fully investigated in haemodialysis patients. Therefore, we compared the effects of gabapentin and pregabalin on intensity of pain and associated HR-QoL in haemodialysis patients with PPN. Methods: Gabapentin and pregabalin were administered after each haemodialysis session at doses of 300 and 75 mg, respectively. Patients were randomized into two groups; after 6 weeks patients underwent a 2-week washout and crossover and received another 6 weeks of treatment. All patients underwent electromyography at the outset. The short-form McGill pain questionnaire (SF-MPQ) for assessment of pain, and short-form medical outcomes study for assessment of HR-QoL at baseline and at the end of the study were applied. Results: Forty patients completed the 14-week study period. Gabapentin and pregabalin significantly improved SF-MPQ total scores compared with pretreatment values (mean ± SD) [from 18.9 ± 4.3 to 9.3 ± 4.3 for gabapentin, p < 0.001, and from 18.5 ± 3.9 to 9.8 ± 3.6 for pregabalin, p < 0.001]. There was no significant difference between the study drugs in terms of efficacy against neuropathic pain (p > 0.05). Both gabapentin and pregabalin significantly improved HR-QoL at the end of the study compared with pretreatment scores (p < 0.001). Conclusion: Our results showed strong efficacy of gabapentin and pregabalin on pain intensity in the given doses. HR-QoL was also significantly improved by both drugs. © 2013 Springer International Publishing Switzerland.