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Background: Numerous studies have evaluated the impact of Helicobacter pylori (H. pylori) eradication on the number, severity, and recurrence of migraine attacks. But the association of migraine, H. pylori, and gastrointestinal (GI) presentation is challenging. The aim of the current study was to investigate the correlation between migraine, H. pylori, and peptic ulcers among patients with dyspepsia undergoing upper GI endoscopy. Methods: 305 patients with dyspepsia referring to our endoscopy ward, Shahid Beheshti Hospital affiliated to Qom University of Medical Sciences, Qom, Iran, for upper GI endoscopy filled out the study questionnaire. If a patient was experiencing headaches and the migraine was confirmed by neurologists, he/she was asked to answer the questions related to migraine, which were prepared exactly from Migraine Disability Assessment (MIDAS) questionnaire. The relation between migraine and confirmed H. pylori contamination was investigated using statistical models. Results: Of all the 305 patients, 133 (43.6%) had confirmed episodic migraine headaches (MHs) and 177 patients (58.04%) had positive RUT for confirming H. pylori contamination, of which 123 (69.5%) had confirmed migraine. 52 (17.0%) had duodenal peptic ulcer(s), of which, 49 (94.2%) had a positive rapid urease test (RUT) (P < 0.001). 20 (6.5%) of all patients had the gastric peptic ulcer(s) which did not have a significant relation with H. pylori contamination. There was a significant relationship between the peptic ulcer site and migraine. In total, 177 patients (58.0%) had a positive RUT. History of migraine was significantly positive in those with positive H. Pylori contamination. Notably, multivariable analysis demonstrated a significant relation of H. pylori and migraine at younger ages. Conclusion: The prevalence of H. pylori and migraine in patients with dyspepsia seems to be high. Moreover, there is a meaningful association between migraine, duodenal peptic ulcers, and H. pylori infection, too. [ABSTRACT FROM AUTHOR]