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Background Gastric juice is usually discarded during upper-GI endoscopy. Objective By using a novel device, the Mt 21-42, we evaluated the potential of this important organic fluid in clinical practice, exploring its contribution to the diagnosis of Helicobacter pylori infection and atrophic gastritis of the oxyntic mucosa (AGOM). Design and Patients A multicenter study (17,907 patients; 10 endoscopy units) estimated the frequency of diagnosis of AGOM and H pylori infection in routine endoscopic practice. A prospective study (216 patients) at 1 of these units aimed to determine the real prevalence of these conditions and the possible benefits of gastric juice analysis. We considered gastric juice pH and ammonium concentration, endoscopic and histologic features, serologic parameters for atrophy and H pylori , gastric acid secretion, and costs. Results We found that H pylori infection and, even more markedly, AGOM were greatly underdiagnosed in routine endoscopic practice (20.1% and 0.8% vs 49.1% and 12.5% in the prospective study, respectively), because of the intrinsic limitations of the conventional tests and lack/inappropriateness of biopsy planning. Gastric-juice analysis proved to be a cheap, simple, and effective way to prevent such underdiagnosis and allowed detection of atrophic gastritis and H pylori in 96% and 98% of cases, and saved costs (cost-effectiveness ratio 209 vs 274-5047). Conclusions Gastric juice provided a valuable source of clinicopathologic information that, properly analyzed, allowed detection of the main risk factors for gastric cancer ( H pylori and atrophic gastritis), overcoming the diagnostic limitations associated with these conditions and also producing time and cost savings.