Background: Because of the prevalence of migraine headaches, it is necessary to study the preventive effect of the drugs which currently are in use for this disease. Therefore, this clinical study was conducted to compare the effects of cyproheptadine and phenytoin on frequency, duration and intensity of migraine headaches in 5-15 year-old children who referred to Neurology Clinic in Sharekurd during 2003.Materials and Methods: In this clinical trial, 119 patients were diagnosed to have migraine on the basis of Headache Classification Committee of International Headache Society criteria. They were later placed in three groups. The study was conducted in three phases. Each phase took 45 days. In the phases 1 and 3 of the study all patients received placebos. In phase two, group one received cyproheptadine (0.3 mg/kg/day), group two phenytoin (4 mg/kg/day) and group three placebos. Throughout the study patients were free to use acetaminophen-codeine on migraine attacks. The intensity of pain was recorded according to the MIDAS questionnaire scaled from 1 to 10 degrees. The result were analyzed by Kruskal - Wallis and Mann - Whitney statistical tests.Results: Compared with phase one, in both drug groups the frequency, duration and intensity of attacks was decreased in the phase two of the study (P<0.05). In cyproheptadine, but not in phenytoin group, the frequency, duration and intensity of attacks were less in phase three compared with phase one (P<0.05). Cyproheptadine was more effective on the frequency, duration and intensity of attacks than phenytoin in phase two of the study. Conclusion: Compared with phenytoin, cyproheptadine seems to be a preferred drug for migraine attacks in children.