The aim of this study was to compare probiotic therapy using a highly concentrated probiotic preparation versus placebo in the ability to prevent the onset of acute pouchitis (inflammation of an ileal pouch–anal anastomosis) during the first year after ileal pouch–anal anastomosis. A total of 40 consecutive patients that underwent ileal pouch–anal anastomosis for ulcerative colitis were randomised to receive either verum (one packet containing 900 billion bacteria/day) (n = 20) or an identical placebo (n = 20) immediately after ileostomy closure for 1 year. The patients were assessed clinically, endoscopically, and histologically after 1, 3, 6, 9 and 12 months. Health-related quality of life was assessed using the Inflammatory Bowel Disease Questionnaire. Two of the 20 patients (10%) treated with verum had an episode of acute pouchitis compared with eight of the 20 patients (40%) treated with placebo. Treatment with verum was associated with a significant improvement in Inflammatory Bowel Disease Questionnaire score, whereas this was not the case with placebo.