Background: Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin hasbeen demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonistduring daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant inpatients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy).Materials and Methods: Twenty patients with HNC were prospectively studied who received a triple antiemeticregimen comprising granisetron (40μg/kg on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125mg on day 1 and 80mg on days 2-5) with FP therapy (cisplatin 20 mg/m2 on days 1-4; 5-FU 400 mg/m2 on days1-5) (aprepitant group). We also retrospectively studied another 20 HNC patients who received the same regimenexcept for aprepitant (control group). Results: For efficacy endpoints based on nausea, the aprepitant groupshowed significantly better results, including a higher rate of complete response (no vomiting and no salvagetherapy) for the acute phase (p=0.0342), although there was no marked difference between the two groups withregard to percentage of patients in whom vomiting was suppressed. There were no clinically relevant adversereactions to aprepitant. Conclusions: This study suggested that a triple antiemetic regimen containing aprepitantis safe and effective for HNC patients receiving daily cisplatin therapy.