NSAID use has been shown to exacerbate disease activity of inflammatory bowel disease. The detrimental effect of NSAIDs on the ileal pouch has not been characterized. To study the effect of withdrawal of NSAID use on ileal pouch disorders. The study consisted of a cohort of 17 symptomatic patients seen in the Pouchitis Clinic who had ulcerative colitis and ileal pouch-anal anastomosis with chronic (>6 months) daily use of NSAIDs. The patients were treated by withdrawing NSAID use. The Pouchitis Disease Activity Index (PDAI) consisting of symptom, endoscopy and histology scores, and Cleveland Global Quality of Life, Irritable Bowel Disease Quality of Life, and Short Inflammatory Bowel Disease Questionnaire scores were measured before and after a 4-week intervention. The cohort consisted of 11 patients with chronic refractory pouchitis (65%), 2 with acute pouchitis (12%), 1 with cuffitis (6%), 1 with cuffitis and chronic refractory pouchitis (6%), and 2 with irritable pouch syndrome (12%). The withdrawal of NSAID use alone resulted in a significant reduction in the mean PDAI scores of -3.6 +/- -3.0 (p<0.02) and a significant improvement in mean quality-of-life scores (p<0.05). Patients with pouch disorders who regularly used NSAIDs appeared to benefit from the complete cessation of such agents, suggesting an association between NSAID use and pouch disorders.