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In patients undergoing craniotomy, the incidence of postoperative nausea and vomiting (PONV) is 55% to 70% and that of moderate to severe postoperative pain is 60% to 84%. We hypothesized that gabapentin plus dexamethasone would be superior, compared with placebo and dexamethasone in reducing the incidences of PONV and pain after craniotomy.Patients undergoing craniotomy received either placebo (group D) or gabapentin (600 mg) (group GD) premedication orally, 2 hours before induction of anesthesia. In addition, all patients received 4 mg of intravenous dexamethasone on the morning of surgery and continued receiving it after every 8 hours. The 24-hour incidence of nausea, emesis, or PONV (nausea, emesis, or both) (primary outcome) and postoperative pain scores (secondary outcome) were analyzed with the χ2 test and the Wilcoxon rank-sum test as applicable.A significant difference was observed between the groups in the incidence of nausea (odds ratio [OR], 0.23; 95% confidence interval [CI], 0.07, 0.80; P=0.02), PONV (OR, 0.3; 95% CI, 0.08, 0.8; P=0.02), and the requirement for antiemetics (OR, 0.30; 95% CI, 0.09, 0.9; P=0.03). The number of emetic episodes were also reduced in group GD, but this did not assume statistical significance (OR, 0.34; 95% CI, 0.10, 1.1; P=0.06). However, there was no significant difference in either the postoperative pain scores or the opioid consumption between the 2 groups.A dosage of 600 mg of gabapentin plus 4 mg of dexamethasone significantly reduced the 24-hour incidence of nausea and PONV. However, there was no reduction in either the postoperative pain scores or opioid consumption.