Purpose Homozygous polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and resultant hyperhomocysteinaemia have been established as an independent risk factor for vascular diseases. There are evidences that vascular abnormalities are involved in the pathogenesis and progression of normaltension glaucoma (NTG). In the present study, we were to find out the associations between 677C4T and 1298A4C polymorphisms of the MTHFR gene and NTG. Methods This was a retrospective, casecontrolled study enrolling 78 NTG patients and 100 controls. DNA from peripheral blood lymphocytes was extracted and the genotypes of polymorphisms (677C4T and 1298A4C) in the MTHFR gene were determined using PCR followed by restriction enzyme digestion. The frequencies of the polymorphic genotypes in the patients with NTG and controls were compared. Results The frequencies of the polymorphisms of the MTHFR gene (677C4T and 1298A4C) in the NTG patients were not significantly different from those of controls. But the younger NTG patients (age at diagnosis p45 years) showed significantly higher prevalence of 677C4T polymorphism than the older NTG patients (age at diagnosis 445 years) (TT genotype, 38.9 vs 11.9%, P ¼ 0.006, OR ¼ 4.71, 95% CI ¼ 1.49-14.9) and than the younger control subgroup (TT genotype, 38.9 vs 6.1%, P ¼ 0.001, OR ¼ 9.86, 95% CI ¼ 2.23-42.4). Conclusions The 677C4T polymorphism was significantly associated with NTG in the younger patients, while 1298A4C polymorphism was not. This suggests that 677C4T polymorphism of the MTHFR gene can be a genetic risk factor of NTG in Korean population.