Introduction: The anesthesia goals for transsphenoidal pituitary surgeries include intraoperative hemodynamic stability and early postoperative recovery for cranial nerve evaluation. In this study, we aim to compare the intraoperative hemodynamics and postoperative recovery of sevoflurane with desflurane in a dexmedetomidine-based general anesthesia. Materials and methods: Sixty patients, 18 to 65 years, American Society of Anesthesiologists (ASA) grades I and II, with Glasgow Coma Scale 15/15 were included. Thirty patients each were randomly divided into group S (sevoflurane) and group D (desflurane). The primary objective was to compare the intraoperative hemodynamics. Secondary objectives were to assess the total dose of dexmedetomidine, number of propofol doses, time to extubate, agitation score at emergence, and modified Aldrete score. The anesthesia management included an intravenous induction followed by maintenance with inhalational agent in oxygen: Nitrous oxide mixture (50%), dexmedetomidine infusion, and rescue doses of propofol. Results: Heart rate (HR) and mean arterial pressure (MAP) were similar in both the groups except MAP just 5 minutes postincision, which was higher in group S (p < 0.001). There were no differences in intraoperative dexmedetomidine use, propofol bolus doses or time to extubate. But the agitation score was higher in group S (p < 0.001). The modified Aldrete score was higher in group D at 5, 15, 30, and 60 minutes (p < 0.001). Conclusion: Both desflurane and sevoflurane produce a similar intraoperative hemodynamic response in a dexmedetomidinebased general anesthesia except sevoflurane, in the doses used in our study was insufficient to attenuate the hypertensive response to incision. With regard to emergence agitation and recovery profile, desflurane appears to be a superior agent.