Abstract: Objective To determine the efficacy of aprepitant on cisplatin-induced nausea and vomiting in melanoma patients. Methods A total of 170 patients who received cisplatin treatment, were assigned randomly into aprepitant group and control group for the prevention of nausea and vomiting. The severity of nausea and vomiting were observed during the 120h post-cisplatin, as well as salvage treatment, functional living index-emesis, and other adverse effect. Results Eighty-four patients were evaluable in each group. Aprepitant group and control group showed an overall complete response rates of 69% and 44% (χ²=10.683, P=0.001). While the incidence of vomiting was much lower in aprepitant group than that in control goup (27% vs. 51%, χ²=9.982, P=0.002). Aprepitant-related adverse effect was not detected in the aprepitant group. Conclusion Antiemetic therapy with aprepitant improves the control of vomiting prevention in melanoma patients receiving cisplatin-based chemotherapy. Although aprepitant is safe, potential drug-drug interactions need to be considered before prescription.