Design: Validation cross-sectional study. Objectives: Even though caregiver burden (CB) represents a well-recognised concern among caregivers of people with a spinal cord injury (SCI), there are no specific questionnaires designed for its evaluation. This study aimed to assess the psychometric properties of the Caregiver Burden Inventory in Spinal Cord Injury (CBI-SCI), which was modified from its original version, and specifically its construct and reliability. Setting: Multicentre study in four urban spinal units across Italy. The CBI-SCI was administered to family caregivers in outpatient clinics.Methods: CBI-SCI was administered in a toolset composed of a sociodemographic questionnaire, the Family Strain Questionnaire-Short Form (FSQ-SF), the Short Form-36 (SF-36), and the Modified Barthel Index (MBI). The CBI-SCI construct validity was assessed through an exploratory factor analysis. The internal consistency of the questionnaire was examined using Cronbach's alpha (α) coefficient for the total scale and its subscales. Concurrent validity was evaluated performing Pearson's correlation coefficient with all instruments included in the toolset. Results: The CBI-SCI was administered to 176 participants from February 2016 to September 2017. Factor analysis highlighted the five-factored structure of the questionnaire. The total scale Cronbach's α was 0.91 (p < 0.001). All the five subscales of CBI-SCI showed an acceptable internal consistency, ranging from 0.76 to 0.91 (p < 0.001). Pearson's correlation coefficients of the CBI-SCI with all the administered instruments were statistically significant (p < 0.001), showing congruent relations. Conclusion: The CBI-SCI, due to its validity and reliability, may represent a valuable instrument to evaluate the CB longitudinally in SCI.