Background/Aim: A recent survey has shown that insomnia is still a very common problem in maintenance hemodialysis (MHD) patients. The aim of the present study was to test the effects of zaleplon (ZAL), a new nonbenzodiazepine hypnotic drug, on the sleep quality of MHD patients with insomnia. Methods: The sleep quality was assessed by the Pittsburgh questionnaire in 10 patients (6 males/4 females) with insomnia on MHD; these patients underwent a randomized double-blind crossover study versus placebo (PLA). The main exclusion criterion was the presence of any possible cause of insomnia related to other concurrent diseases. Results: Treatment with ZAL significantly improved the total score of sleep quality (p < 0.03 vs. PLA). The analysis of the single components revealed that treatment with ZAL was associated with a higher subjective sleep quality (p < 0.01 vs. PLA) and a reduced sleep latency (p < 0.01 vs. PLA). The duration of sleep was not modified by ZAL, whereas a significant improvement was detected in habitual sleep efficacy (p < 0.05 vs. PLA). No peculiar side effect was recorded on ZAL. Blood parameters did not change, nor were differences recorded in the dialysis parameters (body weight gain, blood pressure) throughout the study. Conclusions: This study suggests that ZAL has a positive effect on the sleep quality in MHD patients. The absence of side effects and its pharmacodynamic properties make ZAL a useful drug in uremic patients.