We tested the safety and antiemetic effectiveness of intravenous (IV) dexamethasone (DXM) as an adjunct to high-dose IV metoclopramide (MCP) to prevent nausea and vomiting induced by high-dose cisplatin chemotherapy. Response was determined by using objective and subjective criteria. Thirty patients were randomly assigned to receive MCP alone at a dose of 2 mg/kg IV for three doses or the same dose of MCP plus 20 mg of DXM IV for three doses. Twenty evaluable patients received a second course of cisplatin and were crossed over to the opposite arm. Study results did not show a statistically significant advantage of combination MCP plus DXM over MCP alone using strict objective criteria for antiemetic response. However, patients subjectively preferred MCP plus DXM over MCP alone by nearly a 6:1 ratio, regardless of the randomization sequence. Although the addition of DXM does not appear to objectively improve emetic protection with high-dose MCP, we recommend MCP plus DXM to prevent nausea and vomiting induced by high-dose cisplatin chemotherapy when the use of steroids is not contraindicated, in view of patient preference for the combination.