Background:Gabapentin is an adjuvant antiepileptic agent and helps to reduce acute postoperative pain in several surgery settings. However, the effect of gabapentin on postoperative pain from suboccipital or subtemporal craniotomy is not clear.Methods:The study was a single-center, randomized, placebo-controlled, and double-blinded trial. A total of 122 patients undergoing elective craniotomy by a suboccipital or subtemporal approach were randomly allocated to a placebo group and gabapentin group. The patients received gabapentin (600 mg, orally) the night before surgery and 2 hours before anesthesia induction in the gabapentin group, and patients received vitamin B in the placebo group. The primary outcome was the postoperative pain score on movement at 24 hours. The secondary outcomes included the pain score at other time points, incidence of nausea and vomiting, sedation, and analgesic consumption.Results:Gabapentin significantly decreased the postoperative acute pain scores at rest (P=0.001) and on movement (P=0.000) within 24 hours; however, it did not have an effect at 48 hours. Gabapentin decreased postoperative vomiting (P=0.047) and rescue antiemetic use (P=0.033), whereas it increased the postoperative sedation score at 2 hours (P<0.05). Moreover, gabapentin decreased the mean consumption of intraoperative propofol (0.7 mg/kg/h; P=0.021) and remifentanil (1.3 g/kg/h; P=0.025); however, it did not influence postoperative opioid consumption.Conclusions:Preoperative gabapentin significantly alleviated acute postoperative pain and decreased the incidence of vomiting in patients undergoing suboccipital or subtemporal craniotomy. However, more attention should be paid to early postoperative sedation when multimodal analgesia with gabapentin is administered. © 2019 Wolters Kluwer Health, Inc. All rights reserved.