We designed a multicenter, double-blind randomized study to determine the safety and antiemetic effectiveness of intravenous (IV) methylprednisolone (P) combined with high-dose IV metoclopramide (MTC) v MTC alone in 200 untreated cancer patients receiving cisplatin chemotherapy. One hundred eighty-five patients were evaluable for treatment efficacy. MTC plus P was significantly superior to MTC alone in reducing the number and length of vomiting episodes (P = .001 and P = .0008, respectively) and the maximal intensity of nausea (P = .0124 with a score system; P = .0155 with a linear analogue scale) and length of nausea (P = .0056). The subgroup with a major incidence of nausea and vomiting was women, especially young women, outpatients, and those treated with higher doses of cisplatin. Side effects were low and equally distributed between the two treatment groups. We conclude that MTC plus P has greater antiemetic activity than MTC alone in patients receiving cisplatin chemotherapy.