The overall aim of this study is to better understand important aspects of Carpal Tunnel Syndrome (CTS), a common disabling condition affecting working populations. The study consists of four major aims. In Aim 1, we will measure work and personal risk factors for CTS and other outcomes by extending follow-up of an existing inception cohort of 1100 newly hired workers in diverse jobs. Extended follow-up of this cohort to 7-9 years will increase our ability to study time-dependent events and interactions between work-related and other risk factors for this complex, multi-factorial disease. Data includes measurement of nerve conduction values, workplace physical exposures, psychosocial factors, demographic and anthropometric variables, and concurrent medical conditions. In Aim 2, we will study a new cohort of 800 construction workers, a group at high risk for CTS, to describe the natural history of CTS including outcomes of symptoms, functional status, nerve conduction changes, work disability, and economic impact. In Aim 3, we will ascertain all diagnosed cases of CTS and other upper extremity musculoskeletal disorders in a group of union construction workers, by combining workers' compensation insurance records and personal health insurance data. In Aim 4, we will compare the cumulative incidence of CTS in 1600 truck assembly plant workers with and without baseline abnormalities of median nerve conduction, in order to test the predictive validity and cost-effectiveness of post- offer pre-placement (POPP) nerve conduction studies as a prevention strategy for CTS. In summary, this proposed study of CTS includes 7-9 year follow-up of an existing large cohort with detailed exposure and outcomes data at an individual level. It will contribute to the understanding of the etiology, long-term outcomes, and prevention of CTS. The proposed study will address other important gaps in existing knowledge, including the natural history of CTS, the impact of CTS on work and functional outcomes, and the utility of current screening programs in industry. These four aims represent an important extension of the work done under our current grant, and an opportunity to leverage unique research resources: a large, well- characterized inception cohort; an experienced, multidisciplinary study team; enthusiastic support from union and employer partners providing research access to new cohorts. Public Health Relevance: Carpal tunnel syndrome (CTS) is a common and disabling condition that is related to personal factors such as age and obesity, as well as to workplace factors such as intensive use of the hands. Our study will allow us to better understand how these personal and workplace factors act together to cause CTS. We will also study workers with CTS to learn more about the symptoms and work disability they encounter, and will evaluate a common screening practice used by some employers to identify people who may be at higher risk of CTS.