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Background: The Spinal Cord Independence Measure (SCIM III) is a scale of independence in the activities of daily life, specifically designed for spinal cord injury subjects., Aim: The aim of this study was to calculate the minimal clinically important difference (MCID) of the SCIM III according to distribution and anchor based approach., Design: Prospective study., Setting: Four Spinal Cord Units in Italy., Population: Patients with acute/subacute spinal cord injury/lesion., Methods: The scores of the total SCIM and of the four subscale was recorded at admission and discharge. Clinical significance was calculated according to anchor based methodology using a global rating of change questionnaire. The accuracy of MCID values in predicting a judgment of small improvement by the patients has been assessed by means of the area under the receiving operating curves (aROC)., Results: Total SCIM MCID values varied from 12 for patients with complete tetraplegia to 45.3 for those with incomplete thoracic lesions. The MCID of self-care varied from 3.3 to 8.5 and from 10 to 18 for respiration and sphincter management, depending on the level and severity of the lesion. With regard to mobility (room and toilet), the MCID varied from 1 to 3 and from 2.5 to 7.26 for mobility (indoors and outdoors). The aROC was between good and excellent for all these values., Conclusions: The results provide benchmarks for clinicians and researchers to interpret whether patients' change score on the SCIM III can be interpreted as true or clinically meaningful and to make clinical judgments about the patients' progress., Clinical Rehabilitation Impact: Our data could be useful for both clinicians and researchers. At the beginning of rehabilitation clinicians may have an idea of the minimal improvement of the patient (based on his neurological status) that could have an impact on patient's life. At the end of rehabilitation process, it is possible to control if the patient achieved an improvement that is true and significant. Researchers could also use these criteria to evaluate the clinical significance of an intervention by calculating the number of subjects in the treatment and control groups (or in two different treatment groups) who achieved a change calculated as the natural recovery plus the MCID.