SUMMARYBackground and aims: In a recent open trial we have shown the efficacy of long term intermittent administration of a poorly absorbable antibiotic (rifaximin) in obtaining symptomatic relief in uncomplicated diverticular disease of the colon. The aim of this double‐blind placebo‐controlled trial was to test our previous observations.Methods: One hundred and sixty‐eight outpatients with symptomatic uncomplicated diverticular disease were treated with fibre supplementation (glucomannan 2 g/day) plus rifaximin 400 mg b.d. for 7 days every month (84 patients), or with glucomannan 2 g/day plus placebo two tablets b.d. for 7 days every month (84 patients). Clinical evaluation was performed at admission and at three‐month intervals for 12 months.Results: After 12 months, 68.9 % of the patients treated with rifaximin were symptom‐free or mildly symptomatic, compared to 39.5% in the placebo group (P= 0.001). Symptoms such as bloating and abdominal pain or discomfort were primarily affected by antibiotic treatment when compared with placebo (P<0.001).Conclusion: Rifaximin appears to be of some advantage in obtaining symptomatic relief in diverticular disease of the colon when compared with fibre supplementat