To estimate the clinical and economic effects of available invasive and noninvasive management strategies for peptic ulcer and Helicobacter pylori in persons with symptoms suggesting peptic ulcer disease. Cost-effectiveness analysis using a decision analytic model. 2 immediate endoscopy and 3 noninvasive diagnostic and treatment strategies were evaluated: 1) immediate endoscopy for peptic ulcer and biopsy for H. pylori; 2) immediate endoscopy without biopsy; 3) serologic test for H. pylori; 4) empiric treatment with antisecretory therapy; and 5) empiric treatment with antisecretory therapy and antibiotic agents to eradicate H. pylori. Cost per ulcer cured and cost per patient treated. The estimated costs per ulcer cured by strategy were as follows: 1) endoscopy and biopsy for H. pylori, $8045; 2) endoscopy without biopsy, $6984; 3) serologic test for H. pylori, $4541; 4) empiric antisecretory therapy, $4835; and 5) empiric antisecretory and antibiotic therapy, $4155. The predicted costs per patient treated were as follows: 1) endoscopy and biopsy for H. pylori, $1584; 2) endoscopy without biopsy, $1375; 3) serologic test for H. pylori, $894; 4) empiric antisecretory therapy, $952; and 5) empiric antisecretory and antibiotic therapy, $818. The cost-effectiveness advantage of the noninvasive strategies diminished as the cost of endoscopy decreased or as the probability of recurrent symptoms increased in patients initially managed without endoscopy. Endoscopy, although costly, precisely guided diagnosis and treatment and thus potentially reduced the number of patients inappropriately treated. However, the safety and effectiveness of less expensive, less invasive diagnostic and treatment strategies strongly support initial noninvasive care of symptomatic persons thought to have peptic ulcer disease.