BACKGROUND & AIMS: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Most patients have relapsing disease, and no maintenance treatment study has been performed. We evaluated the efficacy of a probiotic preparation (VSL#3) containing 5 x 10(11) per gram of viable lyophilized bacteria of 4 strains of lactobacilli, 3 strains of bifidobacteria, and 1 strain of Streptococcus salivarius subsp. thermophilus compared with placebo in maintenance of remission of chronic pouchitis. METHODS: Forty patients in clinical and endoscopic remission were randomized to receive either VSL#3, 6 g/day, or an identical placebo for 9 months. Patients were assessed clinically every month and endoscopically and histologically every 2 months or in the case of a relapse. Fecal samples were collected for stool culture before and after antibiotic treatment and each month during maintenance treatment. RESULTS: Three patients (15%) in the VSL#3 group had relapses within the 9-month follow-up period, compared with 20 (100%) in the placebo group (P < 0.001). Fecal concentration of lactobacilli, bifidobacteria, and S. thermophilus increased significantly from baseline levels only in the VSL#3-treated group (P < 0.01). CONCLUSIONS: These results suggest that oral administration of this new probiotic preparation is effective in preventing flare-ups of chronic pouchitis.