OBJECTIVE Gastric cancer, as the fourth most frequent malignancy worldwide, has the highest rate among cancer-related disorders in Ardabil province, located in North-West Iran. Methylene tetrahydrofolate reductase is one of the cancer susceptibility genes with considerable polymorphisms. Methylene tetrahydrofolate reductase C677T leads to a decrease of about 30% in its product activity and is reported to have an effect on cancer susceptibility. METHODS Methylene tetrahydrofolate reductase C677T genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on peripheral blood DNA from 76 gastric cancer patients and 91 healthy controls. The statistical significance was calculated by logistic regression analysis. RESULTS The mean age was 64.2±11.1 and 62.1±9.8 years for cases and controls, respectively. Among tumors, 35.5% were diffuse type and others were intestinal. The frequency of genotypes was 61.8%, 32.9%, and 5.3% among cases and 45.1%, 50.6%, and 4.4% among controls for Ala/Ala, Ala/Val, and Val/Val, respectively. CT heterozygotes had lower susceptibility to gastric cancer (p=0.02). This relationship of significance was detected considering gender and age. CONCLUSIONS It was found that T allele has a protective association with age in the Ardabil province.