Studies of the angiotensin converting enzyme (ACE) I/D polymorphism have provided evidence that the D/D genotype is associated with gastric tumor progression and numbers of lymph node metastases, but not with the overall risk of gastric cancer. The highest levels of circulating and tissue ACE activity were found in carriers of the D/D genotype. Here, we further investigated the association using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The ACE polymorphism was not found to be linked with H. pylori seropositivity or gastric atrophy. However, among H. pylori seropositive subjects with atrophy, those with the I/D genotype had an increased risk of gastric cancer (OR=1.59; 95% CI, 1.02-2.48). We also established that the polymorphism did not lower the age at diagnosis of gastric cancer. Confirmation of the association between ACE polymorphisms and development of gastric cancer requires much larger studies, and the biological role also needs to be fully elucidated.