Background: Between 2001 and 2010, six research groups conducted coordinated multiyear, prospective studies of carpal tunnel syndrome (CTS) incidence in US workers from various industries and collected detailed subject-level exposure information with follow-up symptom, physical examination, electrophysiological measures and job changes. Objective: This analysis of the pooled cohort examined the incidence of dominant-hand CTS in relation to demographic characteristics and estimated associations with occupational psychosocial factors and years worked, adjusting for confounding by personal risk factors. Methods: 3515 participants, without baseline CTS, were followed-up to 7 years. Case criteria included symptoms and an electrodiagnostic study consistent with CTS. Adjusted HRs were estimated in Cox proportional hazard models. Workplace biomechanical factors were collected but not evaluated in this analysis. Results: Women were at elevated risk for CTS (HR=1.30; 95% CI 0.98 to 1.72), and the incidence of CTS increased linearly with both age and body mass index (BMI) over most of the observed range. High job strain increased risk (HR=1.86; 95% CI 1.11 to 3.14), and social support was protective (HR=0.54; 95% CI 0.31 to 0.95). There was an inverse relationship with years worked among recent hires with the highest incidence in the first 3.5 years of work (HR=3.08; 95% CI 1.55 to 6.12). Conclusions: Personal factors associated with an increased risk of developing CTS were BMI, age and being a woman. Workplace risk factors were high job strain, while social support was protective. The inverse relationship between CTS incidence and years worked among recent hires suggests the presence of a healthy worker survivor effect in the cohort.