Purposes: Ondansetron plus dexamethasone are standard antiemetic agents for highly emetogenic chemotherapy. Metoclopramide is a dopamine antagonist, which may enhance efficacy of ondansetron and dexamethasone. The objective of this study was to assess the efficacy and tolerability of metoclopramide added to standard antiemetic regimen for prophylaxis of cisplatin-induced emesis. Methods: Patients who received 50mg/m(2) of cisplatin for the first time were given intravenous ondansetron and dexamethasone on day1 and were randomized to receive either standard antiemetics (ondansetron 8mg orally bid on days2-5 and dexamethasone 8mg orally bid on days2-4) plus metoclopramide 20mg orally qid on days2-5 or a placebo. The primary endpoint was a complete response (CR) rate defined as no emesis and no rescue treatment over a 120-h period. Secondary endpoints included severity of nausea and vomiting, time to first emesis, quality of life, and adverse effects. Results: Among 162 patients, 50 patients (60%) in the metoclopramide group and 42 patients (53%) in the control group achieved CR (p=0.36). The mean times to first emesis in the metoclopramide and control groups were 88 and 75h, respectively (p=0.18). The degrees of nausea and vomiting in both groups were similar. Eleven patients (13%) in the metoclopramide group and 20 (25%) in the control group required rescue treatment (p=0.05). Quality of life and adverse effects were not different between the two groups. Conclusion: The addition of metoclopramide to ondansetron plus dexamethasone reduced the use of rescue medication, but did not affect complete response rate, quality of life or adverse effects.