Recurrence is the most common complication of pericarditis, affecting 10% to 50% of patients. To evaluate the efficacy and safety of colchicine for the secondary prevention of recurrent pericarditis. Prospective, randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov registration number: NCT00128414) SETTING: 4 general hospitals in urban areas of Italy. 120 patients with a first recurrence of pericarditis. In addition to conventional treatment, patients were randomly assigned to receive either placebo or colchicine, 1.0 to 2.0 mg on the first day followed by a maintenance dose of 0.5 to 1.0 mg/d, for 6 months. The primary study end point was the recurrence rate at 18 months. Secondary end points were symptom persistence at 72 hours, remission rate at 1 week, number of recurrences, time to first recurrence, disease-related hospitalization, cardiac tamponade, and rate of constrictive pericarditis. At 18 months, the recurrence rate was 24% in the colchicine group and 55% in the placebo group (absolute risk reduction, 0.31 95% CI, 0.13 to 0.46; relative risk reduction, 0.56 CI, 0.27 to 0.73; number needed to treat, 3 CI, 2 to 7). Colchicine reduced the persistence of symptoms at 72 hours (absolute risk reduction, 0.30 CI, 0.13 to 0.45; relative risk reduction, 0.56 CI, 0.27 to 0.74) and mean number of recurrences, increased the remission rate at 1 week, and prolonged the time to subsequent recurrence. The study groups had similar rates of side effects and drug withdrawal. Multiple recurrences and neoplastic or bacterial causes were excluded. Colchicine is safe and effective for secondary prevention of recurrent pericarditis.