OBJECTIVE: The aim of this study was to determine whether treatment for Helicobacter pylori (H. pylori) for patients with dyspepsia or a history of peptic ulcer decreases hospital expenditures. METHODS: Patients receiving acid suppressive medications were interviewed. Those with a documented ulcer, a self-reported ulcer, or dyspepsia were tested for H. pylori and treated with antibiotics if seropositive. Acid suppressive medications were stopped on completion of H. pylori therapy unless there was a history of gastroesophageal reflux disease (GERD) or Barrett's esophagus, and were started again at the discretion of primary care providers. Total hospital costs and GI medication costs in the 12 months before H. pylori treatment were compared to costs 12 months after H. pylori treatment. RESULTS: A total of 432 consecutive patients were treated for H. pylori. Of the patients, 125 (29%) had dyspepsia, 45 (10%) documented peptic ulcer, and 262 (61%) self-reported peptic ulcer. Total costs (mean 327 US dollars +/- 349 vs 291 USA dollars +/- 362, p = 0.06) and medication costs (mean 207 US dollars +/- 237 vs 224 US dollars +/- 277, p = 0.38) were not significantly different after treatment versus before treatment. A significant decrease in expenditures was limited to patients chronically on acid suppressive medications who had documented peptic ulcers and no history of GERD or Barrett's esophagus (mean 482 US dollars +/- 274 vs 282 US dollars +/- 218, p = 0.03). CONCLUSIONS: Treatment of H. pylori for patients with chronic dyspepsia or self-reported peptic ulcer does not reduce expenditures over 1 yr of follow up. H. pylori treatment for patients chronically receiving acid suppressive treatment with a prior documented ulcer significantly reduces expenditures if GERD and Barrett's esophagus are absent.