Objectives: Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10mg/d flunarizine for CM prophylaxis as compared with 50 mg/d topiramate. Methods: We conducted a prospective, randomized, open--label, blinded--endpoint trial. Patients with CM were randomized to flunarizine and topiramate treatment. The primary outcomes assessed were the reductions in the total numbers of headache days and migraine days after 8 weeks of treatment. Secondary outcomes were reductions in the numbers of days of acute abortive medication intake and acute abortive medication tablets taken, and the 50% responder rate. Results: Sixty--two subjects were randomized (n= 31/group). Patients treated with flunarizine showed significant reductions in the numbers of total headache days (-4.9 vs -2.3, P=. 012) and migraine days (-4.3 vs -1.4, P=. 001) compared with those treated with topiramate. Patients treated with flunarizine also showed significant reductions in the numbers of days of acute abortive medication intake (-2.3 vs -0.2, P=. 005) and acute abortive medication tablets taken (-4.6 vs - 0.5, P=. 005) and had a higher 50% responder rate in terms of total headache days (58.6% vs 25.9%, P=. 013) and migraine days (75.9% vs 29.6%, P=. 001), compared with topiramate--treated patients. Flunarizine was generally well tolerated and had a safety profile comparable to that of topiramate. Conclusions: Our results suggest that, in an 8--week study, 10 mg/d flunarizine is more effective than 50 mg/d topiramate for CM prophylaxis.