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This study aims to evaluate the effectiveness of inpatient and day hospital treatment in German university departments of Psychosomatic Medicine and Psychotherapy in a prospective, naturalistic, multicenter design including structured assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Structured interviews were used to diagnose mental disorders according to ICD-10 and DSM-IV at baseline. Depression, anxiety, somatization, eating disorder and posttraumatic stress disorder (PTSD) symptoms, as well as personality functioning were assessed by means of questionnaires on admission and at discharge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>2,094 patients recruited by 19 participating university hospitals consented to participation in the study. Effect sizes for each of the outcome criteria were calculated for 4\u20135 sub-groups per outcome domain with differing severity at baseline. Pre-post effect sizes for patients with moderate and high symptom severity at baseline ranged from <jats:italic>d<\/jats:italic> = 0.78 to <jats:italic>d<\/jats:italic> = 3.61 with symptoms of PTSD, depression, and anxiety showing the largest and somatization as well as personality functioning showing somewhat smaller effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inpatient and day hospital treatment in German university departments of Psychosomatic Medicine and Psychotherapy is effective under field conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:ext-link>https:\/\/drks.de\/search\/de\/trial\/DRKS00016412<\/jats:ext-link>, identifier: 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