Background: Migraine is considered the end phenotype of a number of polygenic disorders reflecting the influence of several genetic loci modulating different pathophysiological processes. It has been shown that the 677T allele in methylenetetrahydrofolate reductase (MTHFR) gene is directly correlated with decreased enzymatic activity, and the T/T genotype is indirectly associated with mild hyperhomocysteinaemia which possibly leads to vascular disease. In this case-control study we investigated the association between C677T MTHFR polymorphisms and migraine in an Iranian population. Methods: A total of 205 cases and controls were enrolled to the study. The MTHFR C677T variant was genotyped in 102 unrelated migraine cases and 103 controls by HRM-PCR technique. Findings: There was no significant association between C677T MTHFR polymorphism and migraine in our study. The frequency of TT genotype was not higher in case group compared with the controls (OR = 0.667, 95% CI: 0.188-2.362, P = 0.530). Conclusion: The C677T variant in the MTHFR gene did not influence susceptibility to migraine in our study population. A more reliable conclusion may be drawn from investigations with larger sample size and separated migraine groups, with and without aura. Keywords: Genetic polymorphism, Migraine disorders, Methylenetetrahydrofolate reductase