The present study was performed to evaluate the efficacy of low-dose topiramate and compare it with sodium valproate that is prevalently prescribed as a migraine prophylaxis. This was a randomized, double-blind, parallel-group clinical trial on 56 patients who completed the course of study. Topiramate and valproate were administered at 50 mg/day and 400 mg/day, respectively, during the follow-up period. Frequency, intensity, duration, associated symptoms with headaches, analgesics use, as well as drugs' side effects were studied. Participants completed MIDAS and HIT-6 questionnaires before and after treatment. Frequency, intensity, and duration of migraine headaches as well as MIDAS score and symptomatic medications decreased significantly between repeated follow-up visits in both groups. Responder rate for patients treated with topiramate and valproate were 71.6% and 64.3%, respectively, and the difference between the two groups was not statistically significant. The reduction of headache severity in the topiramate group was significantly more than that in the valproate group (p = .027). During the study, no statistically significant reduction in associated symptoms with migraine were observed in both the groups. Topiramate dose of 50 mg/day with fewer side effects in comparison with its higher doses may be an appropriate substitution for first-line migraine prophylaxis such as valproate.