AIM: To assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection. METHODS: Clinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively. RESULTS: A total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia. Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps. Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps. There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection. CONCLUSIONS: The mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection.