Context Accumulating evidence has showed the possibility of using NK1R antagonists for the treatment of chronic pruritus. However, the benefit and risk profile of NK1R antagonists- serlopitant and aprepitant for the treatment of pruritus remains unclear. To assess the efficacy and safety of NK1R antagonists- serlopitant and aprepitant in patients with pruritus based on analysis of clinical trials. The current systematic review and meta-analysis was performed according to PRISMA guidelines. A total of ten randomized clinical trials including 631 patients were enrolled. Four randomized controlled trials investigated the comparative treatment effect of serlopitant on pruritus. Our results showed that serlopitant had reasonable anti-pruritic effectiveness in patients, with mild toxicities. The overall proportion of 4-point improvement of NRS and VAS in serlopitant-treatment group were both significantly higher relative to placebo group (OR 2.345, 95%CI 1.557 to 3.531, P < 0.001; OR 3.308, 95% CI 1.949 to 5.616, P < 0.001). Serlopitant treatment was also found to be associated with a significant reduction in NRS score as compared with placebo (SMD -0.381, 95%CI -0.599 to -0.164, P = 0.001). Six clinical trials reported the treatment effect of aprepitant on pruritus. The meta-analysis result of fixed-effect model showed that there was no significant difference between aprepitant and controlled treatment in terms of improved pruritus VAS score (SMD -0.088, 95%CI -0.384 to 0.207, P = 0.558). There is promising high-quality evidence regarding the efficacy of serlopitant on pruritus. More large-sample randomized controlled trials with appropriate treatment regimen are urgently needed to further evaluate the effectiveness of aprepitant in pruritus. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.