Abstract: This study was conducted to compare the prophylactic activity of propranolol and amitriptyline on frequency, duration and severity of migraine attacks. The rebound effects of these drugs were also evaluated. In a clinical study 105 patients were randomly allocated to one of three groups. The study was divided into three phases, each phase 45 days. In the first phase all patients received two tablet/day, placebo. In the second phase, group one received propranolol (40 mg, twice per day), group two amitriptyline (25 mg, twice per day) and group three continued to receive placebo. In the third phase of the study, all patients received placebo. Patients were free to have acetaminophen-codeine on migraine attacks. All patients were given diagnostic headache diaries in which to record frequency, duration and intensity of attacks. Propranolol and amitriptyline significantly reduced the frequency, duration and intensity of attacks. In contrast to propranolol group, there was a rebound effect following discontinuation of amitriptyline. It seems that propranolol has a therapeutic activity (other then a prophylactic effect) on migraine attacks, however, amitriptyline has only a prophylactic effect.