The use of stress management psychotherapy is hypothesized to produce greater improvement in disease course and disease-specific quality of life (IBDQ) compared to usual medical care alone in patients with ulcerative colitis (UC) or Crohn's disease (CD) showing high levels of stress (based on the Perceived Stress Questionnaire [PSQ]). Fifty-eight patients with UC and 56 patients with CD who had experienced continuous disease activity or had relapsed over the previous 18 months, with an activity index for UC or CD ≥ 4, a PSQ ≥ 60, and without serious psychiatric disorders or other serious medical conditions were randomized to receive either treatment as usual (TAU) or TAU plus stress management psychotherapy. Psychotherapy consisted of three group sessions (psychoeducation, problem-solving, relaxation) and 6-9 individual sessions based on cognitive behavior therapy-related methods with 1-3 booster sessions at 6 and 12 months follow-up. Gastroenterologists blinded to intervention group assessed disease activity and course at baseline and at 3, 6, 12, and 18 months. Patients completed the IBDQ at baseline, 6, 12, and 18 months. The intervention did not improve disease or reduce relapse; however, it increased the IBDQ score (P = 0.009, mean differences 16.3 [SD 6.1]). On analysis of UC and CD separately, improvement of IBDQ was only found in the UC group. Stress management psychotherapy does not appear to improve disease course or reduce relapse in patients with IBD. It might improve quality of life, particularly in patients with UC. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.