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Background and purpose: Pruritus is one of the common problems in hemodialysis patients with end stage renal disease. Approximately, 60% of these patients suffer from this condition. There are several causes for pruritus, thus, various treatments are applied in order to control it. The aim of this study was to evaluate the therapeutic effect of capsaicin on pruritus, compared with placebo, in hemodialysis patients. Materials and methods: This randomized double blind cross over clinical trial study, was performed on 34 hemodialysis patients with uremic pruritus in 1386. All patients were divided in two groups. One group received Caspian 0.03%, while the other, placebo for four weeks. Treatment was stopped for two weeks and continued as cross over technique. Pruritus scores were analyzed with Paired t-test and Repeated measurement ANOVA. Results: In this study, the difference between Mean of pruritus score before capsian treatment and in weeks following 1 to 4 was statistically significant (P=0.0001). In placebo group, the difference between pruritus score before treatment and in weeks 1 to 4 was statistically significant (P=0.0001). There was no significant difference before treatment in two groups, however, after each week, the difference was significant (P=0.0001). Repeated measurement test showed that reduction in pruritus severity in capsian group was more than placebo group, during treatment period (P=0.0001). Conclusion: Although our study indicated the appropriate effects of Capsian in pruritus, the placebo also has a good effect in controlling hemodialysis related pruritus. Our placebo had emollient property; therefore, we can apply it to control the pruritus in these patients. [ABSTRACT FROM AUTHOR]