VacA was histochemically stained in biopsy specimen and was intracellularly an d mainly located in fundic gland area. It is recognized gastric atrophy was obse rved in the H. pylori-positive patients with intracellular VacA compared with o thers.The aim of study is to understand the relationship between intracellular V acA and the progression of gastric atrophy that is associated with gastric cance r. Biopsy specimens and sera were obtained from 364 people in their 50s and 60s without gastric cancer diagnosed at first endoscopy undergoing diagnostic endosc opy, for H. pylori infection, histology, and the histochemical status of intrace llular VacA using anti-VacA Ab during the follow-up period (mean, 7.3 years). Three hundred eleven of 364 enrolled patients were H. pylori positive and 53 pat ients were H. pylori negative at first endoscopy. VacA was intracellularly stain ed with vacuolation and cell de struction in the fundic gland in 98 of 311 H. pylori-positive patients and no t stained in another 213 H. pylori-positive patients plus 53 H.pylori-negative patients at first endoscopy. Gastric atrophy has significantly progressed in th e H. pylori-positive patints with intracellular VacA with gastric ulcers compar ed with the others and six gastric cancers have developed in this group during t he follow-up period (mean, 7.3 years). Intracellular VacA is a valuable marker to predict whether Helicobacter pylori induces progressive atrophic gastritis th at is associated with the development of gastric cancer. VacA was histochemically stained in biopsy specimen and was intracellularly an d major located in fundic gland area. It is recognized gastric atrophy was obseved in the H. pylori-positive patients with intracellular VacA compared with o thers. Aim of study is to understand the relationship between intracellular V acA and the progression of gastric atrophy that is associated with gastric canceration. Biopsy specimens and sera were obtained from 364 people in their 50s and 60s without gastric cancer diagnosed at first endoscopy undergoing diagnostic endoscopic, for H. pylori infection, histology, and the histochemical status of intracelular VacA using anti-VacA Ab during the follow-up period (mean, 7.3 years). Three hundred eleven of 364 enrolled patients were H. pylori positive and 53 patients were H. pylori negative at first endoscopy. VacA was intracellularly stain ed with vacuolation and cell detruction in the fundic gland in 98 of 311 H. pylori-positive patients and no t stai ned in another 213 H. pylori-positive patients plus 53 H. pylori-negative patients at first endoscopy. Gastric atrophy has significantly progressed in th e H. pylori-positive patints with intracellular VacA with gastric ulcers compar ed with the others and six gastric cancers have developed in this group during t he follow-up period (mean, 7.3 years). Intracellular VacA is a valuable marker to predict whether Helicobacter pylori induces progressive atrophic gastritis th at is associated with the development of gastric cancer.