Aging and smoking are known to promote atrophic gastritis (AG) and intestinal metaplasia (IM). This study investigated the relationship between Helicobacter pylori (Hp) infection, aging, smoking, and AG/IM. Ninety-six Hp-negative and 231 Hp-positive subjects were divided according to age; (< or = 39 years, 40-59 years, and > or = 60 years) and smoking history (never smoked, or currently smoking). Histologic grading was performed according to the updated Sydney system. Fasting pH, total bile acid (TBA) concentration, and ammonia (NH3) concentration in gastric juice were measured. Comparisons were made based on Hp status, age, and smoking. Independent relative risks for severe AG and IM were calculated. Grades of atrophy and IM were significantly higher in Hp-positive subjects, and these increased with age. Within Hp-positive subjects, grades of atrophy and IM were higher in smokers and in the middle and upper age groups. Within Hp-positive subjects, gastric pH and TBA were similarly higher in smokers and older subjects. An increased risk of severe AG/IM was statistically associated with smoking (OR 9.31, 3.85-22.50/OR 4.91, 1.90-12.68) and high TBA concentrations (OR 2.92, 1.19-7.17/OR 3.28, 1.25-8.62). Both Hp infection and aging are closely related to the development of AG and IM. Cigarette use and high TBA concentrations may play a role in the progression of AG and IM in Hp-positive subjects.