ED is prevalent in hemodialysis (HD) patients, and closely related to poor sleep and depression. Efficacy of treating ED either with sildenafil or vardenafil has been shown to be beneficial in ameliorating concomitant depression in non-HD patients. It is yet to be shown whether treatment of ED with a PDE-5 inhibitor would improve poor sleep in HD patients. We aimed to compare the effects of sildenafil and vardenafil on sleep quality and depression in HD patients with ED. A total of 32 maintenance HD patients with ED randomized into two groups to receive either sildenafil or vardenafil for 4 weeks. After a 2-week washout and a crossover, each group received the other drug for another 4-week period. Sleep quality and depression were evaluated via post-sleep inventory (PSI) and Beck's depression inventory (BDI), respectively, at baseline and at the end of the treatment. Sildenafil and vardenafil both improved PSI and BDI scores significantly compared with pretreatment values. However, there was no difference between sildenafil and vardenafil with respect to these parameters. PDE-5 inhibitors, sildenafil and vardenafil, caused a significant improvement in sleep quality and depression in this cohort of HD patients with ED.