Background: In clinical trials of Irritable Bowel Syndrome (IBS), evaluation of treatment efficacy is still mainly subjective. We compared three outcome measures in reflecting response to treatment in a clinical trial of IBS.Materials and Methods: Sixty three adult IBS patients participated in a placebo-controlled trial of 10-wk cognitive-behavioral therapy. Patients completed .the IBS-quality of Life questionnaire (IBS-QOL), IBS-symptom severity scale (IBS-SSS), extra-intestinal symptom severity scale (EISSS), and Hospital Anxiety and Depression Scale (HADS) before and after the intervention. After the intervention, patients responded to the IBS-Adequate Relied (IBS-AR) and IBS-Global Assessment of Improvement (IBS-GAI) instruments. Patients were categorized into responders and non-responders based on each of the IBS-AR, IBS-GAI, and IBS-SSS instruments. Quality of life, IBS and extra-intestinal symptoms severity, anxiety, and depression scores were compared-between the responders and non-responders.Results: Forty six patients (mean age 31.5±6.9 years, 82.6% female) completed the study. After the intervention, significant correlations were found between responder definitions results (r=0.385 to 0.689, P<0.001). Compared with IBS-AR and IBS-GAI, defining responders based on the IBS-SSS instrument was related to more reduction in severities of IBS and extra-intestinal symptoms, anxiety, and depression scores and to more increase in quality of life scores.Conclusion: The IBS-SSS instrument is more comprehensive in reflecting changes in symptoms severity, quality of life,-and psychological status compared with other outcome measures. IBS-AR is accepted as the current standard for evaluating the efficacy of IBS treatments, however, we recommend IBS-SSS to be applied as well.