Abstract Background Scientific data indicates that in the course of Crohn’s disease (CD), certain endoscopic abnormalities in the upper gastrointestinal tract (UGIT), such as bamboo joint-like appearance (BJA) in the stomach, may be frequently present. However, there are not many clinical analyses available, in which prevalence of various endoscopic UGIT lesions would be comprehensively evaluated. The purpose of the study was to investigate the characteristic of UGIT involvement in CD, with a particular focus on the Helicobacter pylori (Hp) status, BJA lesions and presence of microscopic changes in the stomach. Methods A total of 565 consecutive patients were prospectively recruited into the study (98 with CD and 467 controls). All individuals underwent upper esophagogastroduodenoscopy (EGD) with biopsy using a high definition endoscope with narrow band image. Chi-square and t-student tests were used for statistical analysis. Results The majority of CD patients (n=77; 79%) were found to have different abnormalities in EGD. Most commonly these were found in the stomach (n = 73; 74%), followed by duodenum (n= 39; 40%) and oesophagus (n=6; 6%). Mucosal redness/edema, BJA in the proximal part of the body and/or fundus, as well as antral erosions were the most prevalent gastric lesions. BJA was present in 44 (45%) of CD patients, and in one individual from the control group (0.002%), p<0.00001. BJA presence among CD patients was irrespective of sex, age, location, duration, intensity or course of the disease, as well as medications taken. Ulcerations and erosions were most commonly found lesions in the duodenum. Most of the CD patients were Hp negative (n = 94; 95.9%), while in the control group the majority of individuals were infected with Hp (57,1%), p<0.0001. Comparison between Hp negative patients with CD and controls revealed that gastric BJA lesions, duodenal ulcers and erosions were present exclusively in CD. These lesions were accompanied by chronic microscopic gastritis in all cases. Finally, the prevalence of microscopic HP negative gastritis was significantly higher in patients with CD than in controls (95.7% vs 15%, p<0.0002). Conclusion Our results demonstrated that chronic Hp negative gastritis is present in nearly all CD patients, and is strongly associated with presence of gastric BJA lesions, as well as ulcerations and erosions of the duodenum. Furthermore, the results of our study support previously reported observations that BJA is a specific lesion for CD and may be used as an endoscopic diagnostic marker. This work was financed by the Program of the Minister of Science and Higher Education - “Regional Initiative of Excellence” in 2019–2022, no. 002/RID/2018/19.