OBJECTIVE : Studies suggest that peptic ulcer and periodontal disease are positively associated with bladder cancer risk. These two factors are likely to share common biologic mechanisms such as inflammation and dysbiosis. We examined the joint association of peptic ulcer (gastric/duodenal) and periodontal disease on bladder cancer risk. METHODS : We conducted a prospective analysis among 45,185 men (563 invasive bladder cancer cases) in the Health Professionals Follow-Up Study (follow-up 1986-2016). History of ulcer and periodontal disease was self-reported at baseline and updated during the follow-up. Cox proportional hazards models estimated hazard ratio (HR) and 95% confidence interval (CI) for the joint associations of ulcers (gastric, duodenal) and periodontal disease, adjusting for age and other potential confounders. We tested for interaction using the Wald test for product terms. RESULTS : Compared with men having no history of ulcer and periodontal disease, men with a history of peptic ulcer only (HR 1.22, 95% CI 0.90-1.66) and men with a history of periodontal disease only (HR 1.19, 95% CI 0.98-1.46) were associated with higher risk of invasive bladder cancer. The highest bladder cancer risk was observed in men with a history of both peptic ulcer and periodontal disease (HR 1.52, 95% CI 1.05-2.20). Similar results were found when we stratified by ulcer types. The interactions between ulcer and periodontal disease were not statistically significant for all ulcer types (p-interaction ≥ 0.59). CONCLUSIONS : We did not find sufficient evidence for interaction between gastric/duodenal ulcers and periodontal disease on bladder cancer risk.