This double-blind, randomized, placebo-controlled study evaluated the minimum effective dose of dexamethasone for postoperative antiemesis. One-hundred fifty women scheduled for major gynecological surgery were randomly assigned to receive dexamethasone 10 mg (D10), 5 mg (D5), 2.5 mg (D2.5), 1.25 mg (D1.25), or placebo (P) before the induction of general anesthesia. A standardized general anesthesia technique was used. Postoperative pain was treated with bolus IV doses of morphine via a patient-controlled analgesia device. Patients were assessed for incidence of vomiting at 4, 8, 12, and 24 h after surgery. A total of 6, 6, 8, 15, and 19 patients in Groups D10, D5, D2.5, D1.25, and Group P experienced vomiting at least once within the first postoperative 24 h, respectively. Dexamethasone 10 mg, 5 mg, and 2.5 mg was more effective than dexamethasone 1.25 mg or placebo for antiemesis (P < 0.05). The difference in antiemetic effect among the 10 mg, 5 mg, and 2.5 mg groups was similar. The results suggest that 2.5 mg is the minimum effective dose of dexamethasone for postoperative antiemesis in patients undergoing general anesthesia for major gynecological surgery. Implications: Although dexamethasone is effective for antiemesis, major side effects may accompany its perioperative use. To achieve the best antiemesis with the fewest side effects, dexamethasone 10 mg, 5 mg, 2.5 mg, and 1.25 mg were compared with placebo in surgical patients. We found 2.5 mg to be the minimum effective dose without discernible side effects.