Study Design Cross-sectional. Introduction Pain severity, sensory and motor impairment, and psychological (distress and anxiety) and social factors have previously been related to self-reported disability in persons with wrist and hand pain. Purpose of the study The purpose of this study to determine the relative contribution of pain severity, measures of impairment (sensory and motor function), psychosocial factors, and pain interference on self-reported disability experienced by persons with heterogeneous orthopedic injuries and conditions of the wrist and hand. Methods Measures of disability and pain severity as well as measures of sensory (pressure pain thresholds, joint position sense), motor (grip strength, Purdue pegboard), and cognitive performance (Stroop test) and psychosocial variables related to pain and participation (West Haven-Yale Multidimensional Pain Inventory) were administered to 60 participants with wrist and hand pain. Pearson product correlations controlled for age and sex, and multiple linear regression was performed to determine the relationship between measures of impairment, pain severity, psychosocial variables, and pain interference with self-reported disability assessed with the Disability of Arm, Shoulder and Hand (DASH) questionnaire. Results The best-fitting regression model with DASH scores entered as the dependent variable (F4,50 = 28.8, P Conclusion Pain interference appears to be an important factor explaining the link between impairment, pain severity, and self-reported disability. Addressing pain interference may be important to improve outcomes in this population.