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Anesthesia for craniotomies should blunt responses to noxious stimuli, whereas subsequently leaving patients sufficiently alert for early neurological evaluation. The aim was to compare postoperative blood pressure control, pain, and opioid requirement after anesthesia with dexmedetomidine versus remifentanil. We therefore tested 2 primary hypotheses: (1) intraoperative administration of dexmedetomidine provides better control of postoperative blood pressure than remifentanil; and (2) patients given dexmedetomidine have less postoperative pain and use less opioid.Adults having elective brain tumor excisions under balanced general anesthesia with endotracheal intubation were randomized to an infusion of remifentanil (0.08 to 0.15 μg/kg/min, n=71) or dexmedetomidine (0.2 to 0.7 μg/kg/h, n=68). Patients also received propofol, rocuronium, fentanyl, and sevoflurane. The mean arterial pressure (MAP) and pain were recorded at 15, 30, 45, 60, and 90 postoperative minutes. Outcomes were assessed with joint hypothesis testing, evaluating noninferiority and superiority.Compared with remifentanil, the use of dexmedetomidine was associated with reduced postoperative MAP (88±12 vs. 98±11 mm Hg), with estimated mean difference (97.5% confidence interval) of −10 (−13, −4) mm Hg, P<0.001, and mean visual analog pain score (2.9±2.6 vs. 5.1±2.4 points), with estimated mean difference of −5 (−10, −3) points, P<0.001, and required less median opioid consumption (5 [0, 10] vs. 10 [7, 15] mg morphine equivalents), with estimated median difference of −5 (−10, −3) mg, P<0.001. Dexmedetomidine was both noninferior and superior to remifentanil in maintaining postoperative hemodynamics and providing improved pain control.Intraoperative dexmedetomidine better controlled postoperative MAP and provided superior analgesia in patients undergoing craniotomy.