OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic disorder of brain-gut interaction. Previous studies suggest that mindfulness could be therapeutic for IBS patients, however no study has evaluated the effects of mindfulness-based cognitive therapy adapted for patients with IBS (MBCT-IBS). A 6-week MBCT-IBS course was designed to reduce symptoms and increase quality of life. This study aimed to evaluate the effects of MBCT-IBS and to investigate its therapeutic mechanisms in a randomized controlled trial. METHOD: Sixty-seven female patients with IBS were randomized to MBCT-IBS (MG; n = 36) or a waitlist (WL; n = 31) control condition. Patients completed standardized self-report measures of IBS symptom severity, IBS quality of life, maladaptive illness cognitions (catastrophizing, visceral anxiety sensitivity) and mindfulness at baseline, after 2 treatment sessions, at posttreatment, and at 6-week follow-up. Self-referential processing of illness and health was measured with an implicit association test (IAT). RESULTS: The MG reported significantly greater reductions in IBS symptoms (p = .003) and improvements in quality of life (p < .001) at follow-up compared with the WL. Changes in visceral anxiety sensitivity and pain catastrophizing at posttreatment and reductions in the IAT-score after 2 sessions combined with increases in nonjudgmental awareness at posttreatment mediated reductions in IBS symptoms. CONCLUSIONS: MBCT-IBS has the potential to reduce IBS symptoms and increase quality of life. MBCT-IBS may exert its effect on IBS symptoms via reducing maladaptive illness cognitions and activating changes in self-processing (reducing biases in self-referent processing of illness and health and increasing nonjudgmental awareness). (PsycINFO Database Record (c) 2020 APA, all rights reserved).