INTRODUCTION: Irritable bowel syndrome (IBS) is a common and debilitating disorder. When dietary and pharmacological interventions are not satisfactory, psychological treatment may produce good results. However, the access to such treatment is scarce, and therefore, it is of importance to make use of technical solutions. In this study, we wanted to investigate the real-world effectiveness of an Internet-delivered exposure-based cognitive behavior therapy (ECBT) for IBS and to replicate an earlier finding regarding the working mechanism of the treatment. METHODS: A total of 309 consecutively recruited patients from the Internet Psychiatry Clinic in Stockholm received ECBT for 12 weeks. The patients' IBS symptoms, quality of life, avoidance behaviors, and gastrointestinal symptom-specific anxiety were monitored, and we used a bivariate cross-lagged panel model to investigate time-related change in symptoms and avoidance behaviors. RESULTS: IBS symptoms, measured with the Gastrointestinal Symptom Rating Scale for IBS, were reduced from 48.06 (SD = 11.26) before treatment to 33.06 (SD = 10.81) 6 months after treatment (P < 0.001). The effect size (calculated by Cohen d) was 1.30 (1.08-1.51). There was a significant (P < 0.001) cross-lagged effect from reduction in avoidance behavior to reduction in symptoms but not in the reverse direction, indicating that the treatment effect is mediated by behavioral change. DISCUSSION: We conclude that ECBT is effective under real-world conditions, also when delivered through the Internet, and that an important treatment mechanism is the reduction of avoidance behaviors.