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The aim of the present study was to assess the relationship between change in interpersonal difficulties with change in chronic pain, health status and psychological state in 257 irritable bowel syndrome (IBS) patients in a randomized control trial comparing psychotherapy, antidepressant and usual care. We assessed at three time points interpersonal problems (IIP-32), abdominal pain and bowel symptoms, psychological distress (SCL-90), and health status (SF-36). Analysis included repeated measures (ANOVA) to assess change over time and multiple regressions to identify whether change in IIP was associated with outcome after controlling for psychological status. The main findings were: (1) difficulties with social inhibition and dependency were associated with longer disease duration; (2) change in mean IIP-32 over 15 months was significantly correlated with changes in pain, but these relationships were mediated by change in psychological distress; (3) change in IIP-32 was an independent predictor of improved health status at 15 months only in the psychotherapy group. These results indicate that improvement in interpersonal problems in IBS patients appear to be primarily associated with reduced psychological distress but, in addition, the association with improved health status following psychotherapy suggests that specific help with interpersonal problems may play a role in improving health status of patients with chronic painful IBS.