Background: This study evaluated the validity of the factor structure of the Disabilities of the Arm, Shoulder and Hand questionnaire to assess upper extremity disability in patients with upper extremity nerve injury. Methods: Data were used from previous cross-sectional studies of patients with upper extremity nerve injuries. Research ethics approval was obtained for secondary data analyses. Descriptive and factor analyses were performed. Results: Patients (n = 242; 170 men and 72 women) with upper extremity nerve injury included distal nerve (n = 131), brachial plexus (n = 88), and single proximal shoulder nerve (n = 23). The mean Disabilities of the Arm, Shoulder and Hand questionnaire score was 47.3 ± 22. For the questionnaire, a three-factor structure had the highest variance and no overlap between factors. The factors related to (1) light effort tasks, (2) greater effort tasks, and (3) work/social activity limitations and pain. Brachial plexus injuries had significantly higher overall questionnaire scores compared to distal and single proximal nerve injuries. The light effort factor scores were significantly lower in single proximal nerve injuries compared with brachial plexus and distal nerve injuries. Nondominant compared to dominant hand involvement revealed no difference in overall questionnaire scores but significantly higher dominant hand scores in the light effort factor (p = 0.001). Conclusions: In patients with nerve injury, the factor analysis of the Disabilities of the Arm, Shoulder and Hand questionnaire indicated a multifactor construct. These domains should be considered when using the questionnaire and may be helpful to assess disability related to specific tasks in different nerve injuries and with dominant hand involvement.