Ten percent of the American working population is disabled due to workplace injury or illness. This dissertation addresses prevention of upper extremity musculoskeletal disorders and the predictors of long-term disability. Early detection of musculoskeletal disorders is key to successful treatment and to minimize incidence and severity. Disability measures are associated with work status; however, little evaluation has been done in working populations. This study assessed the validity of the QuickDASH disability instrument in a cross-sectional study of 599 full-time workers with upper extremity musculoskeletal symptoms in the previous week. The accuracy of the baseline QuickDASH to identify workers with or likely to develop upper extremity MSD problems at baseline, 4-months, and 1-year. Workers with upper extremity musculoskeletal diagnosis had higher (p<0.001) QuickDASH scores (disability) than those without. A trend of increasing QuickDASH scores with increasing symptom severity category (p<0.001) was observed. There was little correlation between the QuickDASH score and SF-12 physical component score, implying that the two instruments measure different phenomenon. The QuickDASH demonstrated good internal consistency, and accuracy at baseline for musculoskeletal disorder diagnosis, and symptom severity. Receiver operator characteristic curves, sensitivity, specificity, negative and positive predictive values are provided. Study findings support the validity of the QuickDASH to assess upper extremity musculoskeletal disability in working populations. In addition, predictive factors in a workers' compensation system for guiding preventive interventions to high-risk claims were identified. Claims were followed for 6 years in a retrospective cohort study. There was considerable agreement between logistic, quantile regression, and Cox proportional hazards models. The strongest predictors of long-term disability were hospitalized within 28 days of injury, age, interval between injury and treatment, construction industry, logging occupation, gender, and upper extremity non-traumatic musculoskeletal disorders. Early detection of musculoskeletal disorders in the workplace if followed by appropriate preventive interventions like hazard reduction, modified work, recovery time, task rotation or other measures can serve as tools for primary prevention. Secondary prevention efforts including return to work programs, medical management, detailed communication between employees, employers, medical care providers, and insurance agents can be successful in shortening disability time.