Background & Aims: Preventive treatment of migraine headaches is performed after careful and complete examination of the number and quality of headaches in the patient to improve the patient's quality of life and avoid unpleasant side effects. This study was conducted to evaluate the efficacy of two drugs of levetiracetam and sodium valproate on preventive treatment of migraine headaches. Materials & Methods: In this prospective study, 35 patients with migraine headache who met the preventive treatments criteria and underwent at least 12 weeks of sodium valproate treatment at a dose of 1000 mg daily and did not responded to treatment were randomly selected and included in the study and their drug was changed to levetiracetam at a dose of 500 mg daily. All patients were visited 6 weeks and 12 weeks later in terms of the number, severity, duration and quality of headaches and the data was recorded in the relevant forms. Finally, all data was entered into SPSS software and analyzed. Results: 35 patients participated in this study, among which 40% were male and 60% were female. The mean age of the patients was 32. 51 ± 10. 90 years. In this study, according to the results of the repeat measure, it was concluded that levetiracetam drug reduces both the severity and the number of migraine headaches in the patients who have shown resistance to sodium valproate (P = 0. 001). Conclusion: It seems that levetiracetam is an appropriate option to treat migraine headache in the patients who have shown resistance to sodium valproate or the probability of side effects of sodium valproate is high in the disease.