The higher frequency of CT genotype and allele T in POAG indicated that the genotype CT and allele T of MTHFR C677T polymorphism might be associated with susceptibility risk of POAG (RR = 1.91, EF = 0.211) while the decreased frequency of genotype CC in POAG as compared to controls indicated that genotype CC may be resistant to POAG in Saudis. This evidence concerns the gene MTHFR and open-angle glaucoma.