To examine the third version of the Spinal Cord Independence Measure (SCIM III) for reliability and validity in a multi-center cohort study. Four hundred and twenty-five patients with spinal cord lesions from 13 spinal cord units in six countries from three continents were assessed with SCIM III and the Functional Independence measure (FIM) on admission to rehabilitation and before discharge. Total agreement between raters was above 80% in most SCIM III tasks, and all kappa coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.9, and intraclass correlation coefficients were above 0.94. Cronbach's alpha was above 0.7. The coefficient of Pearson correlation between FIM and SCIM III was 0.790 (P<0.01). SCIM III was more responsive to changes than FIM in the subscales of Respiration and sphincter management and Mobility indoors and outdoors. The results support the reliability and validity of SCIM III in a multi-cultural setup. Despite several limitations of the study, the results indicate that SCIM III is an efficient measure for functional assessment of SCL patients and can be safely used for clinical and research trials, including international multi-center studies.