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Abstract Psychological characterization of patients affected by Inflammatory Bowel Disease (IBD) focuses on comorbidity with psychiatric disorders, somatization or alexithymia. Whereas IBD patients had higher risk of stable anxiety and depression for many years after the diagnosis of the disease, there is a lack of studies reporting a comprehensive psychosomatic assessment addressing factors of disease vulnerability, also in the long-term. The objective of this investigation is to fill this gap in the current literature. The aims were thus to assess: a) changes between baseline and a 4-year follow-up in psychiatric diagnoses (SCID), psychosomatic syndromes (DCPR), psychological well-being (PWB-I), lifestyle, gastrointestinal symptoms related to IBD and Irritable Bowel Syndrome (IBS)-like symptoms b) stability of psychiatric and psychosomatic syndromes at 4-year follow-up. A total of 111 IBD outpatients were enrolled; 59.5% of them participated at the follow-up. A comprehensive assessment, including both interviews and self-report questionnaires, was provided at baseline and follow-up. Results showed increased psychiatric diagnoses, physical activity, consumption of vegetables and IBS-like symptoms at follow-up. Additionally, whereas psychiatric diagnoses were no longer present and new psychopathological pictures ensued at follow-up, more than half of the sample maintained psychosomatic syndromes (particularly allostatic overload, type A behavior, demoralization) from baseline to follow-up. Long-term presence/persistence of such psychosocial burden indicates the need for integrating a comprehensive psychosomatic evaluation beyond traditional psychiatric nosography in IBD patients. Moreover, since psychosomatic syndromes represent vulnerability factors of diseases, further studies should target subgroups of patients presenting with persistent psychosomatic syndromes and worse course of the disease.