Balanced anesthesia with sevoflurane-fentanyl has been widely accepted as anesthetic management for neurosurgery. Propofol-remifentanil regimen has been successfully used in various surgical settings, but a comprehensive comparison of sevoflurane-fentanyl and propofol-remifentanil anesthesia in patients undergoing craniotomy for supratentorial intracranial surgery has not yet been done. The aim of this prospective, randomized, open-label clinical trial was to compare clinical properties of sevoflurane-fentanyl with propofol-remifentanil anesthesia in patients undergoing supratentorial intracranial surgery. The primary endpoint was to compare early postoperative recovery and cognitive functions within the two groups; we also evaluated hemodynamic events, vomiting, shivering, and pain. One hundred twenty patients (64 males; age 15-75 years) were randomized to either total intravenous anesthesia (group T) or sevoflurane anesthesia (group S). Emergence and extubation times and cognitive function (Short Orientation Memory Concentration Test [SOMCT]) were compared in the two groups. Brain swelling, incidence of hypotensive and hypertensive episodes, postoperative vomiting, shivering, and pain were also analyzed. The mean emergence time (12.2 ± 4.9 minutes for group S versus 12.3 ± 6.1 minutes for group T; P = 0.92) and extubation time (18.2 ± 2.3 minutes for group S versus 18.3 ± 2.1 minutes for group T; P = 0.80) were similar in the two groups. Average SOMCT scores, both 15 minutes after extubation (25.6 ± 4.9 in group S versus 23.9 ± 7.5 in group T; P = 0.14) and 45 minutes after extubation (27.3 ± 2.2 in group S versus 26.0 ± 5.1 in group T; P = 0.07) were also comparable. Brain swelling was present in seven and five patients in groups S and T, respectively (P = 0.76). Hypotension was present in 12% (group S) and 28% (group T) of patients (P = 0.02). Hypertension was present in 17% of patients in group S and 40% of patients in group T (P = 0.0046). Shivering was present in 18% and 25% of patients in groups T and S (P = 0.37). Our study demonstrates that there is no patient benefit of using total intravenous anesthesia with an ultra-short-acting opioid over the conventional balanced volatile technique in terms of recovery and cognitive functions.