Background: Migraine is a common disease that globally affects about 14% of the population, accounting for 1/3 of the burden of neurological disease. Topiramate is considered one of the first-line options for the prevention of Migraine because of its optimal benefits. Therefore, Vietnam in general and the Mekong Delta, in particular, need more studies to clarify the clinical symptoms of Migraine and evaluate the effectiveness of Topiramate in the treatment of migraine headaches. Objectives: To describe the clinical characteristics of migraine headaches and to evaluate the efficacy and safety of topiramate for migraine prevention. Materials and methods: A cross-sectional descriptive study and clinical intervention without a control group of 70 patients diagnosed with Migraine headaches. Study participants were evaluated for clinical characteristics of Migraine and Topiramate treatment was initiated at 50 mg/day. The primary efficacy measure was defined as ≥ 50% reduction in monthly migraine frequency after 4 weeks, 8 weeks, and 12 weeks. Results: The ratio of female/male: 3/1; mean age 43.5±12.3; the mean age of Migraine onset was 38.9 ± 10.3 with the mean monthly number of Migraine episodes (28 days) being 4.7 ± 1.5. The effective rate of Topiramate in the treatment of Migraine is 86.4%, specifically at doses of Topiramate 50mg, 100mg, 200mg, 40%, 30.5%, and 15.9%, respectively. The main side effects of the drug are weight loss (52.5%), loss of appetite (25.4%), paresthesia (22.1%). There were no serious adverse events or death. Conclusions: Migraine mainly affects women (757%), the age of onset is usually middle-aged. Topiramate treatment at daily doses of approximately 50mg resulted in statistically significant improvements in mean monthly Migraine. Topiramate is safe and well- tolerated in patients with Migraine headaches.