OBJECTIVE To investigate the prevalence and clinical characteristics of Helicobacter pylori (H. pylori)-infected dyspeptic patients with selective immunoglobulin E deficiency (IgEd). METHODS All individuals who underwent serum total immunoglobulin E (IgE) measurement at the Leumit Healthcare Services (Israel) in 2012 were identified in an electronic database search (n = 18487). From these, selected case group subjects were ≥ 12 years of age and had serum total IgE < 2 kIU/L (n = 158). The control group was selected from a random sampling of the remaining subjects ≥ 12 years of age to obtain a case-control ratio of 1:20 (n = 3160). Dyspeptic diseases, diagnosed no more than 5 years before serum total IgE testing, were identified and retrieved from the electronic database using specific International Classification of Diseases diagnostic codes. Results of C(13)-urea breath tests were used to identify subjects infected with H. pylori. Categorical variables between case and control subjects were analyzed using Fisher's exact tests, whereas continuous variables were analyzed using χ (2) tests. RESULTS Dyspepsia was present in 27.2% (43/158) of case subjects and 22.7% (718/3160) of controls. Of these, significantly more case subjects (32/43, 74.4%) than controls (223/718, 31.1%) were positive for H. pylori (P < 0.01). Esophagogastroduodenoscopy was performed in 19 case and 94 control subjects, revealing that gastritis was more prevalent in IgEd case subjects than in controls (57.9% vs 29.8%, P < 0.05). Furthermore, a significantly greater proportion of case subjects presented with peptic duodenal ulcers (63.2% vs 15.9%, P < 0.01). Histopathologic examination showed marked chronic inflammation, lymphoid follicle formation and prominent germinal centers, with polymorphonuclear cell infiltration of gastric glands, that was similar in case and control biopsy tissues. Finally, IgEd case subjects that underwent esophagogastroduodenoscopy were more likely to exhibit treatment-refractory H. pylori infections that require second-line triple antibiotic therapy (47.4% vs 11.7%, P < 0.01). CONCLUSIONS IgEd is associated with higher rates of H. pylori-associated gastritis and peptic duodenal ulcers.