The objective of this study was to identify risk factors for work disability among persons with carpal tunnel syndrome (CTS). The study was designed to analyze data from the Occupational Health Supplement of the National Health Interview Survey, a nationwide, population-based survey. Subjects included 544 survey respondents with self-report of CTS and 32,688 survey respondents without CTS, all aged 18-64 years, and with a history of labor force participation. Measurements were as follows: Dependent variables were work disability, defined either as cessation of employment without attribution of cause or, alternatively, as cessation of employment or job change specifically attributed to CTS by the survey respondent. Independent variables were ergonomic risk of work disability, defined by minutes of workplace repetitive hand and wrist bending for the most recent job held. This measure was derived from responses categorized by an occupation and industry matrix independent of CTS status. Socio-demographic and health status risk factors for work disability were based on the respondent report. The main results were as follows: Among 544 persons with CTS, 58 (11%, CI 8-13%) reported work disability specifically attributed to CTS, representing an estimated national prevalence of 240,578 persons with this limitation. Workplace ergonomic risk, measured as repetitive hand or wrist bending in the occupation and industry of last employment, was a significant factor predictive of CTS-attributed work disability (per 120 min of daily exposure, OR 1.7, CI 1.1-2.6), even after taking into account socio-demographic factors and health status. The conclusions were that work disability among persons with CTS is common. For those with CTS, working conditions characterized by repetitive bending of the hand or wrist may increase the risk of work disability associated with this condition.