AIM: To determine whether Helicobacter pylori (H pylori) infection caused hyperhomocysteinemia by altering serum vitamin B12, serum folate and erythrocyte folate levels and whether eradication of this organism decreased serum homocysteine level. METHODS: The study involved 73 dyspeptic H pylork positive patients, none of them had gastric mucosal atrophy based on rapid urease test and histology. Out of 73 patients, 41 (56.2%) showed a successful eradication of H pylori 4 wk after the end of treatment. In these 41 patients, fasting serum vitamin B12folate and homocysteine levels, and erythrocyte folate levels before and 4 wk after H pylori eradication therapy were compared. RESULTS: The group with a successful eradication of H pylori had significantly higher serum vitamin B12and erythrocyte folate levels in the post-treatment period compared to those in pre-treatment period (210±97 pg/mL vs 237±94 pg/mL,P<0.001 and 442±212 ng/mL vs 539±304 ng/mL, P=0.024, respectively), but showed no significant change in serum folate levels (5.6±2.6 ng/mL vs 6.0+2.4 ng/mL, P=0.341). Also, the serum homocysteine levels in this group were significantly lower after therapy (13.1±5.2 μmol/L vs 11.9±6.2 μmol/L, P=0.002). Regression analysis showed that serum homocysteine level was positively correlated with age (P=0.01) and negatively with serum folate level before therapy (P=0.003). CONCLUSION: Eradication of H pylori decreases serum homocysteine even in patients who do not exhibit gastric mucosal atrophy. It appears that the level of homocysteine in serum is related to a complex interaction among serum vitamin B12, serum folate and erythrocyte folate levels.