Background: Migraine is not curable, but preventive treatments are usually used to decrease the intensity and frequency of headache attacks. Different therapeutic options are widely studied for chronic migraine (CM), but all of them have different inefficacies.Objective: The aim of this study was to compare the efficacy of levetiracetam versus sodium valproate in the treatment of CM. Methods: A randomized controlled clinical trial was conducted on 62 patients with chronic migraine (30 patients in intervention group-treated with levetiracetam and 32 patients in control group- treated with sodium valproate). The treatment regimen consisted of initial dose of levetiracetam or sodium valproate 500 mg daily which increased to 500 mg two times a day after two weeks. The treatment response was evaluated by measuring pain frequency, pain severity, and the MIDAS (migraine disability assessment) score over three months follow-up. Results: During a three-month follow-up, the mean of headache frequency, severity, and MIDAS score were changed significantly. The rate of decrease in headache frequency was higher in control group than intervention group ((6.7±2.7 and 14.4±5.3 day/month, respectively) (P<0.001). Also, headache severity and MIDAS score significantly decreased in the control group than intervention group (3.4±1.1 and 5.7±1.6, respectively P<0.001, 16.7 ± 6.1 and 30.2±9.8, respectively (P<0.001). Conclusions: According to our findings, levetiracetam offered improvement in headache frequency, severity, and MIDAS score in patients with CM. However, levetiracetam was not effective enough for chronic migraine as valproate, despite some significant effect. Thus levetiracetam can be one of the choices for limited chronic migraine subjects who are in contraindication of Valproate.