Crohn's disease (CD) of the pouch can develop in patients with ileal pouch-anal anastomosis, resulting in significant morbidities, even pouch failure. The aim of this study was to evaluate short- and long-term outcome of adalimumab (ADA) in treating these patients.A total of 48 patients who received ADA for CD of the pouch from June 2006 to June 2011 were identified from our prospectively maintained Pouchitis Registry Complete clinical response was defined as the resolution of symptoms as well as the modified Pouchitis Disease Activity Index (mPDAI) score being less than 5. Partial clinical response was defined as improvement in symptoms as well as a reduction in mPDAI score of 2 or more. Endoscopic mucosal healing status before and after therapy was recorded.At a short follow-up of median 8 weeks, 24 (50%) patients had complete response, 10 (21%) had partial response, and 14 (29%) had no response. After a median follow-up of 25.1 months, 16 (33%) patients had a complete response, 10 (21%) had a partial response, and 22 (46%) had no response. At the end of the follow-up, 13 (27%) patients achieved mucosal healing. A total of nine (19%) patients eventually developed pouch failure. Patients with a long-term response had a significantly higher mucosal healing rate (60.9% vs. 28.6%, P = 0.032) and significantly lower median mPDAI score (2.0 vs. 5.0, P = 0.004) at the first follow-up evaluation than those with no long-term response. Multivariate analysis showed concurrent endoscopic stricture dilation (hazard ratio = 5.9; 95% confidence interval: 1.6, 21.2) increased the chance for the long-term response to ADA. One patient developed multiple sclerosis during the therapy.ADA treatment, particularly in conjunction with endoscopic therapy, may help rescue a subgroup of patients with CD of the pouch from having surgery.