BACKGROUND AND AIMS: Recurrence of Crohn's disease (CD) after surgery is a major concern. Curcumin has antiinflammatory properties and induces endoscopic remission in patients with ulcerative colitis. We investigated the efficacy of curcumin vs placebo in preventing post-operative recurrence of CD, based on endoscopic and clinical indices, in patients receiving concomitant thiopurine therapy. METHODS: We conducted a double-blind randomized controlled trial at 8 referral centers in France, from October 2014 through January 2018, of 62 consecutive patients with CD undergoing bowel resection. Patients received azathioprine (2.5 mg/kg) and were randomly assigned to groups given oral curcumin (3 g/day; n = 31) or an identical placebo (n = 31) for 6 months, and were then evaluated by colonoscopy. We also collected data on CD activity index, results from laboratory tests, and answers to quality of life questionnaires during this 6-month period. The primary endpoint was postoperative recurrence of CD in each group (Rutgeerts' index score >= i2) at month 6 (determined by central reading). An interim analysis (intent to treat) was scheduled after 50% of the patients were enrolled. RESULTS: At month 6, postoperative recurrence (Rutgeerts' index score >= i2) occurred in 18 patients (58%) receiving curcumin and 21 patients (68%) receiving placebo (P =.60). A significantly higher proportion of patients receiving curcumin (55%) had a severe recurrence of CD (Rutgeerts' index score >= i3) than patients receiving placebo (26%) (P =.034). We observed a clinical recurrence of CD (CD activity index score > 150) at month 6 in 45% of patients receiving placebo and 30% of patients receiving curcumin (P =.80). Quality of life scores at month 6 did not differ significantly between groups (P =.80). Severe adverse events developed in 6% of patients receiving placebo and 16% of patients receiving curcumin (P =.42). CONCLUSIONS: In a randomized controlled trial of patients who underwent surgery for CD and received thiopurine treatment, we found that curcumin was no more effective than placebo in preventing CD recurrence. There were no significant differences between groups in quality of life or severe adverse events. The study was discontinued after interim analysis due to futility.