Attributable risk models describe the role of three risk factors for peptic ulcer and related serious upper gastrointestinal (GI) events. The factors-nonsteroidal antiinflammatory drugs (NSAIDs), Helicobacter pylori, and cigarette smoking-have been identified as major risk factors for peptic ulcer in numerous clinical and epidemiologic studies. Overall risk ratios for each risk factor were based on meta-analyses of English-language studies of risk for peptic ulcer-related GI events. Exposure estimates for factors used data from North American populations. Summary risk and exposure values were computed for the general population, males and females separately, and the elderly. Hypothetical models of multiple factor attributable risks were developed using population attributable risk percent calculated from these summary values. General population attributable risk percent were as follows: 24%, NSAIDs; 48%, H. pylori; and 23%, cigarette smoking. Based on these numbers, the "no interaction" attributable risk model estimates that 95% of total peptic ulcer related risk is attributable to these factors in the general population. The "interaction" model attributes 89% of cases to these risk factors: 24%, NSAIDs alone; 31%, H. pylori alone; 34%, H. pylori/smoking combined. Between 89% and 95% of peptic ulcer-related serious upper GI events may be attributed to NSAID use, H. pylori infection, and cigarette smoking.