Objective outcome measures are needed to confirm the merits of large-scale health initiatives in the workplace. We used aggregate medical claims data to evaluate the illness experience of 5160 employees during the 2 years after versus the 2 years before an intervention intended to identify, treat, and prevent Helicobacter pylori-related illnesses. Across all participants, a 2.1-fold reduction (95% confidence interval 1.4–3.1) in ulcer-related illness episodes and a marginal 1.1-fold reduction (95% confidence interval 0.9–1.4) in episodes due to other stomach and duodenal diseases were achieved. Improvement in claims experience was most notable among 250 employees with ulcer findings on the screening examination. This H. pylori health initiative appears to have contributed to a cost-effective reduction in subsequent illness episodes due to ulcer and possibly due to other stomach and duodenal disease.