The authors assessed the separate and joint influences of cigarette smoking and Helicobacter pylori infection on the development of gastric cancer in a population-based prospective study. A total of 1,071 Japanese men aged ≥40 years were followed up prospectively for 14 years (1998–2002). Compared with that for current nonsmokers, the multivariate-adjusted hazard ratios of gastric cancer for smokers of 1–9, 10–19, and ≥20 cigarettes per day were 1.36 (95% confidence interval (CI): 0.50, 3.71), 1.93 (95% CI: 1.01, 3.67), and 1.88 (95% CI: 1.02, 3.43), respectively. The risk of gastric cancer increased steeply for subjects who had both a smoking habit and H. pylori infection compared with those who did not have both risk factors (hazard ratio=11.41, 95% CI: 1.54, 84.67). If causal, the estimated population attributable fraction of gastric cancer for cigarette smoking was approximately half that for H. pylori infection (28.4% vs. 56.2%). The overlap of the population attributable fractions for the 2 factors was 49.6%. Findings suggest that cigarette smoking and H. pylori infection are significant risk factors for gastric cancer in Japanese men, and the magnitude of their combined influence is considerable.