Granisetron, a selective 5-hydroxytryptamine 3 antagonist, is effective for the treatment of patients with postoperative nausea and vomiting. Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen.This study compared the efficacy of granisetron alone with granisetron/dexamethasone combination for the treatment of nausea and vomiting after major gynecologic surgery.In this randomized, double-blind study, patients who were experiencing emetic symptoms during 0 to 3 hours after the end of anesthesia administration received granisetron 40 μg/kg IV either alone or in combination with dexamethasone 8 mg. Patients then were observed for 24 hours after study drug administration, with emetic episodes recorded and tolerability assessments performed by nursing staff blinded to treatment.A total of 120 women were enrolled (n = 60 in each treatment group; mean [SD] age in the granisetron group, 44 [9] years [range, 23-63 years]; combination group, 45 [8] years [range, 21-65 years]). No significant differences in patient demographic characteristics were found between the 2 treatment groups. However, the percentage of patients free of emetic symptoms (nausea, retching, vomiting) was higher in the granisetron/dexamethasone combination group than in the granisetron group (95.0% and 80.0%, respectively; P = 0.012). No clinically serious adverse events attributed to the study drugs were observed in either group.In this study, the granisetron/dexamethasone combination was more effective than was granisetron alone for the management of nausea and vomiting during 0 to 3 hours after anesthesia in women undergoing major gynecologic surgery.