The purpose of this study was to estimate the incidence of carpal tunnel syndrome (CTS) in a general population according to employment status and to assess the proportion of cases attributable to work. CTS occurring in patients aged 20-59 years living in the French Maine and Loire region were included prospectively from 2002 to 2004. Medical and occupation history was gathered by mailed questionnaire. Incidence rates of CTS and relative risks (RRs) of CTS were computed in relation to employment status. The attributable fractions of risk of CTS to work among the exposed persons (AFEs) were calculated. A total of 1168 patients (819 women, 349 men) were included during the 3-year period. The mean incidence rate of CTS per 1000 person-years was higher in employed than unemployed persons (1.7 vs. 0.8 in women and 0.6 vs. 0.3 in men). The excess risk of CTS was statistically significant for male (RR 4.2) and female (RR 3.0) blue-collar workers and female lower-grade white-collar workers (RR 2.5). The AFE to work in general was 47% (95% confidence interval: 39-54) in women. AFEs reached higher values in female blue-collar workers [67% (65-68)] and lower-grade services, sales, and clerical white-collar workers [61% (57-64)]. The AFE in male blue-collar workers was 76% (72-80). These data show a higher incidence of CTS in the working than the non-working population and suggest that a substantial proportion of CTS cases diagnosed in lower-grade white-collar and blue-collar workers are attributable to work.