Background: Opioid-based anesthetic techniques are commonly used during neurosurgical procedures. In the present randomized prospective study, we studied emergence after 4 anesthetic regimens combining intermediate duration opioids with isoflurane and nitrous oxide (N2O), in patients undergoing craniotomy for large (> 30 mm diameter with intracranial mass effect) intracranial tumors.; Methods: One hundred seven patients were randomized into 4 groups: Group A: fentanyl (<= 5 mu g/kg) + isoflurane (<= 1 minimum alveolar concentration [MAC]), Group B: sufentanil (1-2 mu g/kg plus infusion) + isoflurane (<= 0.5 MAC), Group C: sufentanil (2 mu g/kg bolus only) + isoflurane (<= 1 MAC), and Group D: alfentanil (100 mu g/kg plus infusion) + isoflurane (<= 0.5 MAC). Boluses were administered as divided doses during induction, laryngoscopy, head pinning, and incision. Blood pressure was controlled at 625% of baseline levels. All infusions were discontinued at the start of dural closure. Emergence was assessed using a mini-neurologic examination consisting of 7 questions. Groups were compared on time to emergence using survival analysis methods.; Results: The groups did not differ regarding extubation time, which occurred at a median of 4 to 6 minutes across groups after discontinuing N2O. The median emergence time ranged from 15 to 22.5 minutes and did not differ among groups. However, across all groups more women had emerged by 30 minutes compared with men (83% vs 57%, P =.002). The median emergence time in women was found to be significantly shorter (0-15 minutes) than in men (15-30 minutes) (P =.012).; Conclusions: No between-group differences in emergence time were observed; the study was stopped early because of evidence that no differences were likely to be found if the study were continued. However, in a post hoc analysis, female gender was associated with faster emergence.