OBJECTIVE. We sought to understand the wide range of problems that patients with upper-extremity peripheral nerve disorders experience and to identify predictors of disability and quality of life (QOL). METHOD. Data from standardized assessments of disability and QOL, physical examination results, and intake surveys from 627 patients were analyzed using descriptive and inferential statistics. We compared results between groups and built multivariate models measuring disability, work disability, and physical and mental QOL. RESULTS. The sample demonstrated substantial disability and even greater work disability, which both closely correlated with poorer QOL. Work status was integral in predicting disability. Common predictors across models included problems with sleep and intimate relationships, deficits in work and household performance, and higher pain. CONCLUSION. To decrease disability and improve QOL, occupational therapy practitioners should help patients with upper-extremity peripheral nerve disorders identify strategies to maintain meaningful work and household roles, intimate relationships, and sleep, while continuing to address pain. © 2017, American Occupational Therapy Association, Inc. All rights reserved.