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AIM: Prepouch ileitis (PPI) is inflammation of the ileum proximal to an ileoanal pouch, usually associated with pouchitis. The treatment of PPI as a specific entity has been poorly studied, but it is generally treated concurrently with pouchitis. This to our knowledge is the largest study to explore the efficacy of biologics for the specific treatment of PPI. METHODS: This was a retrospective observational study reporting outcomes following biological treatment in patients with PPI across three centers. Data were collected between January 2004 and February 2018 from two centers in the UK and one center in Italy. Outcomes included the continued presence of PPI following biologic therapy, pouch failure defined by the need for an ileostomy, and remission of PPI defined by the absence of any prepouch inflammation on endoscopic assessment within a year of biologic therapy. RESULTS: There were 29 patients in our cohort. On last endoscopic follow-up, 20/29 still had endoscopic evidence of PPI, seven had achieved endoscopic remission and avoided an ileostomy, and two had no endoscopic follow-up. In our cohort 11 patients had an ileostomy after a median time from starting a biologic of 25 months (range 14-91). CONCLUSION: Biologics fail to induce endoscopic remission of PPI in the majority of patients. Just under one-third patients with PPI coexistent with pouchitis can achieve endoscopic remission with biologics. In a large proportion of patients with PPI, surgery may be required despite biologic use.