Background:Migraine is a chronic disease that affects nearly 6% of men and 18% of women worldwide. There are various drugs, which can successfully decrease migraine symptoms and frequency of migraine attacks, but these drugs usually are expensive. Hence, this study aimed to assess the effects of pyridoxine supplementation on severity, frequency and duration of migraine attacks as well as headache diary results (HDR).Methods:This double-blind randomized clinical trial study was conducted on 66 patients with migraine with aura (MA) in Khorshid and Emam Mosa Sadr clinics of Isfahan University of Medical Sciences, Iran, in 2013. Patients were randomly allocated to receive either pyridoxine supplements (80 mg pyridoxine per day) or placebo. Severity, frequency and duration of migraine attacks and HDR were measured at baseline and at the end of the study.Results:Mean age of patients was 34.24 ± 9.44 years old. Pyridoxine supplementation led to a significant decrease in headache severity (-2.20 ± 1.70 compared with -1 ± 1.50; P = 0.007), attacks duration (-8.30 ± 12.60 compared with -1.70 ± 9.60; P = 0.030) and HDR (-89.70 ± 134.60 compared with -6.10 ± 155.50; P = 0.040) compared with placebo, but was not effective on the frequency of migraine attacks (-2.30 ± 4 compared with -1.20 ± 7.80; P = 0.510).Conclusion:Pyridoxine supplementation in patients with MA was effective on headache severity, attacks duration and HDR, but did not affect the frequency of migraine attacks.