Background: Migraine is a chronic, often debilitating disease. The treatment of migraine with propranolol (80-240 mg/day) is limited by side effects and lack of tolerability. Ribofl avin (vitamin B2) is the precursor of fl avin mononucleotide and fl avin adenine dinucleotide which are involved in mitochondrial transport chain. The use of ribofl avin in migraine prophylaxis is based on the hypothesis of a defi cient mitochondrial energy reserve as a causal factor in migraine pathogenesis, and on the fi ndings of its safety and effectiveness at high doses (400 mg/day) in the treatment of migraine like headaches in classic mitochondriopathies. Objectives: To compare the effi cacy of lower dose oral ribofl avin at 100 mg/day with oral propranolol 80 mg/day in the reduction of migraine frequency and severity. Methods: One hundred patients diagnosed with migraine were randomized to receive either oral ribofl avin 100 mg/day or propranolol 80 mg/day for a period of 3 months. Patients were issued a migraine diary and explained how to record the frequency of migraine attacks, headache intensity, duration and to report any side effects. Follow-up was at the end of 3 and 6 months. Results: Both study groups showed a reduction of migraine frequency, duration and severity of headache by visual analogue scale (VAS), and disability by migraine disability questionnaire (MIDAS) score at 3 months. No signifi cant difference was seen between the two study groups in most of the measures. Side effects were signifi cantly less in the ribofl avin group (P=0.035). Conclusion: Oral ribofl avin 100mg/day is a safe, equally effective and well tolerated alternative in migraine prophylaxis.