Purpose: Chronic granulomatous disease (CGD) is a genetically inherited disorder with a defect in NADPH oxidase of phagocytic cells predisposing to bacterial and fungal infections. Gastrointestinal involvement is seen in about 40% of patients with CGD presenting as an inflammatory bowel disease or motility disorder. Aim: To characterize the endoscopic features and the role of endoscopy in diagnosis and management of gastrointestinal CGD. Methods: A database was created with all patients seen at NIH with CGD. Their clinical, pathologic and endoscopic data was gathered and analyzed. Colitis was defined endoscopically as mild, moderate or severe. Mild disease was characterized by erythema, mucosal friability, nodularity or alteration in vascular pattern. Moderate disease was characterized by erosions, aphthous ulcers or small linear ulcers. Severe disease was characterized by extensive ulcerations with or without complications such as fistulae and strictures. Results: A total of 222 endoscopies: 100 EGDs, 89 colonoscopies and 33 flexible sigmoidoscopies have been performed at NIH, in 81 patients with CGD, between 1990 and 2010. CGD related inflammatory bowel disease, assessed endoscopically, extended from the esophagus to the anus. Esophageal, gastric and duodenal inflammation was seen in 25%, 73% and 39%, respectively, with gastric and duodenal ulcers in 16% and 30%, respectively. Esophageal dysmotility and structural abnormalities were noted in 25% and 29% respectively with only 11% of them being symptomatic. Colonic inflammatory bowel disease characterized by skip lesions was seen in 73% of patients with presence of ano-rectal disease in 96% of patients. Mild, moderate and severe colitis was seen in 17%, 34% and 49% of patients, respectively. CGD related inflammatory bowel disease being a transmural process led to enteric fistulae in 15% of patients with 75% of these being present in the perianal area. Anorectal strictures were noted in 26% patients requiring serial dilations. No patient has developed colonic premalignant lesions or malignancy. Conclusion: Endoscopy helped in characterizing CGD related IBD as a distinct entity which primarily involves the anus and rectum with skip lesions in the remaining bowel. Fistulae and strictures are primarily located in the anorectal area and particular attention needs to be directed towards this area during evaluation of CGD patients. Upper GI tract inflammatory disease is common though not as severe as colonic disease. Endoscopic extent of disease activity and severity helped in guiding medical management, selection of patients for surgical diversion and consideration for hematopoietic stem cell transplantation.