Volatile agents combined with opioids or α2 agonists may reduce inhalation agents concentration or provide optimal hemodynamic stability. We compared the hemodynamic stability brain relaxation, and recovery characteristics of sevoflurane anesthesia supplemented with an infusion of dexmedetomidine or remifentanil in patients undergoing supratentorial craniotomy. We enrolled 80 adult patients in a prospective randomized 2 group study. ASA I-III physical status patients who were undergoing intracranial surgery for either vascular or space-occupying lesions, were eligible if aged 17 to 65 years. Patients were randomly allocated in 2 groups. Anesthesia was induced with thiopental sodium (3 to 7 mg/kg) and remifentanil (0.5μg/kg/min) in remifentanil group. Anesthesia was maintained sevoflurane (maximum 1 MAC) and remifentanil infusion (0.25 μg/kg/min). In the second group (dexmedetomidine group), patients received intravenous dexmedetomidine 0.5μg/kg over 10 minutes. Anesthesia was induced thiopental sodium (3 to 7 mg/kg). Anesthesia was maintained sevoflurane (maximum 1 MAC) and dexmedetomidine infusion (0.6 μg/kg/h). Hemodynamic variables were recorded at baseline, induction of anesthesia, tracheal intubation, head holder application, skin incision, dural incision, and dural closure. Brain relaxation scores were evaluated by surgeon, intraoperatively. Hemodynamic variables were similar between the groups except heart rate. Eye opening, following the verbal commands and orientation time were significantly shorter in patients receiving remifentanil-sevoflurane than the other group. We conclude that any of the 2 anesthetic techniques are acceptable for intracranial surgery. Remifentanil plus sevoflurane anesthesia provide earlier recovery and cognition than the intraoperative use of dexmedetomidine plus sevoflurane anesthesia.