Background: Control of intracranial pressure (ICP) before, during and after neurosurgical operations is crucially important. Therefore, trying different methods and drug combinations to attain this goal is an ongoing effort in anesthesiology. In this study we compared two combinations of a narcotic agent with propofol in neurosurgical operations to control intracranial pressure.Methods: In this prospective randomized double-blind clinical trial, we enrolled 34 patients with supratentorial brain tumors who were candidates for craniotomy in Alzahra Hospital in Isfahan, Iran from April 2008 to April 2009. The patients were randomly divided into two groups of 17, in whom the first and the second group, respectively, received a combination of "propofol and fentanyl" and a combination of "propofol and remifentanyl" as maintenance of anesthesia. The hemodynamic status, ICP during the surgery, and post-surgical complications in recovery unit were observed for and registered in a questionnaire.Results: Hemodynamic status was similar in both groups and they did not differ in recovery complications except for pain which was more prevalent in remifentanil group (P<0.03). Although the patients in fentanyl group better responded to the drug for lowering ICP than remifentanyl group, but the difference was not statistically significant.Conclusion: There is no difference between these two anesthetic agent combinations and both could be useful in the anesthesia of neurosurgical operations. However combination of propofol and fentanyl seem to be superior because of more pain relief and a smoother recovery period.