Objective: Restorative proctolectomy is considered the procedure of choice in patients with ulcerative colitis who have failed medical therapy. Chronic pouchitis occurs in 10%-15% of patients, which often require long-term antibiotics to alleviate symptoms. Safety and efficacy of long-term maintenance antibiotics for chronic pouchitis has yet to be established. We aimed to assess the long-term safety and efficacy of maintenance antibiotic therapy for chronic pouchitis. Design: This was an observational study. We followed up patients who were diagnosed with chronic antibiotic-dependent pouchitis. Setting: Data were collected from our single specialist pouch centre. Patients: Patients with chronic antibiotic-dependent pouchitis who had been maintained on antibiotics continuously for at least 1 year with a least one follow-up visit. Main outcome measure: Development of pouch failure defined by the need for an ileostomy, patient-reported side effects of antibiotics and development of antibiotic resistance found on stool coliform testing. Results: Long-term use of antibiotics achieve remission in 21% of patients over a median follow-up of 102 (range 9-125). Pouch failure in association with chronic pouchitis after a median follow-up of 8.5 years occurred in 18%. Side effects of long-term antibiotic use occurred in 28% of patients, with resistance to antibiotics from at least one stool sample occurring in 78% patients. Conclusions: Although the use of antibiotics in chronic pouchitis may be justified, the use of long-term antibiotics must be weighed against potential complications associated with pouchitis and antibiotics.