Background/aim: Sex-related differences in response to pain have become a topic of increasing interest. However, sex-related differences in the efficacy of dexamethasone for postoperative analgesia have not been previously addressed. Materials and methods: The study included 196 men and 196 women, aged between 18 and 45 years, who were scheduled for laparoscopic cholecystectomy. The patients were randomly allocated into dexamethasone (M/F: 98/98) and control (normal saline; M/F: 98/98) groups. Patients in the study group received intravenous dexamethasone at 0.1 mg/kg (dexamethasone group) 1 h before induction of anesthesia. Patients in the control group received normal saline. Changes in cumulative morphine-containing, patient-controlled analgesia consumption in both sexes, pain intensity using a visual analog scale 24 h after surgery, mean morphine consumption adjusted for body weight, and incidence of postoperative nausea or vomiting were measured. Results: Women in both groups had significantly higher pain scores at 1 and 6 h postoperatively, higher levels of patient-controlled analgesia and mean morphine consumption, and more postoperative nausea and vomiting (P < 0.05). These effects were less severe in the dexamethasone group. Conclusion: The results suggest that women are less responsive than men to dexamethasone for postoperative analgesia and experience higher levels of postoperative pain.