Pouchitis is associated with dysbiosis and dysregulated mucosal immunity, although secondary pouchitis with special etiologic factors, such as ischemia, can occur. The aim was to describe a disease phenotype of the ileal pouch with an endoscopic appearance suggestive of ischemia. We identified consecutive patients with endoscopic asymmetric inflammation of the pouch (inflammation of side of the pouch with a completely normal other limb of the pouch one limb and a sharp demarcation along the staple suture line). Patients with Crohn's disease (CD) of the pouch or antibiotic-responsive pouchitis, matched for duration of the pouch, served as controls. Histology slides of mucosal biopsies were re-reviewed independently by 2 blinded gastrointestinal pathologists. Demographic, clinical, endoscopic, histologic, and imaging characteristics were compared between the groups. Ten patients with "ischemic" pouchitis, 15 with CD of the pouch, and 15 with antibiotic-responsive pouchitis were studied. Pyloric gland metaplasia was observed only in the groups with CD of the pouch (23.1%) or antibiotic-responsive pouchitis (13.3%). Of patients with "ischemic" pouchitis, 80% had extracellular hemosiderin or hematoidin deposits (versus 30.8% those with CD of the pouch and 13.3% of those with pouchitis, P = 0.003). The majority of patients (80%) with "ischemic" pouchitis did not respond to conventional antibiotic therapy. It appeared that subsequent abdominal surgeries after pouch construction and a history of postoperative portal vein thrombi were associated with "ischemic" pouchitis. Endoscopic asymmetric inflammation of the pouch may represent an ischemia-associated pouchitis with characteristic clinical, radiographic, and histologic features. Its hemodynamic, cellular, and molecular basis of mechanism warrants further study.