Background: The relationship between proton pump inhibitor therapy and other acid suppressing medications and the risk of gastrointestinal infections remains controversial. Methods: Patients enrolled in a long-term trial of lansoprazole for Zollinger-Ellison syndrome and other acid hypersecretory states had interval histories taken every six months regarding hospitalizations or other intercurrent medical conditions. All medications taken were also reviewed at each visit. In addition, available patients were specifically queried during the study period 2006-2007 regarding the development of any gastrointestinal infections, hospitalizations, and prescriptions for antibiotics. Results: Ninety patients were enrolled in our long-term study and 81 were available for review. The median basal gastric pH for the cohort after stabilization on therapy was 2.9 and ranged from 1.1-8.4 with a median pentagastrin stimulated gastric pH of 1.60 (range 1.0-8.2). No patient developed a clinically significant gastrointestinal infection during the study. The median patient years of follow-up were 6.25 years. Conclusion: In a cohort of patients with gastric acid hypersecretion inwhom acid secretion status was monitored on lansoprazole, all were free of significant gastrointestinal infections on long-term follow-up. © 2008 Wilcox et al; licensee BioMed Central Ltd.