Aprepitant, an oral neurokinin-1 receptor antagonist, has demonstrated improved control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of aprepitant in patients receiving highly emetogenic chemotherapy (HEC) in Asian countries. This multicenter, double-blind, placebo-controlled trial assessed the prevention of CINV during the acute phase (AP), delayed phase (DP), and overall phase (OP). Patients receiving HEC were randomized to either an aprepitant group (day 1, aprepitant 125 mg; days 2-3, aprepitant 80 mg) or a standard therapy group (days 1-3, placebo). Both groups received intravenous granisetron and oral dexamethasone. The primary end point was complete response (CR; no emesis and no use of rescue therapy) during the OP. Of the 421 randomized patients, 411 (98 %) were assessable for efficacy; 69.6 % (142/204) and 57.0 % (118/207) of patients reported CR during the OP in the aprepitant and standard therapy groups, respectively (P = 0.007). CR rates in the aprepitant group were higher during the DP (74.0 % vs. 59.4 %, P = 0.001) but were similar during the AP (79.4 % vs. 79.3 %, P = 0.942). Toxicity and adverse events were comparable in both groups. The addition of aprepitant to standard antiemetic treatment regimens for Chinese patients undergoing HEC provided superior CINV prevention and was well tolerated.