Carpal tunnel syndrome (CTS) is a common cause of compression neuropathy of the upper extremities. This retrospective nationwide matched cohort study was conducted using the data from the Taiwan National Health Insurance Research Database between January 2003 and December 2012. The incidence rate of CTS was 975.84 and 544.12/100,000 person-years, respectively, yielding an incidence rate ratio of 1.79 (95% confidence interval, 1.68-1.91, P < 0.0001). CTS patients with End-stage renal disease (ESRD) in the dialysis group were more likely to receive surgical intervention than those the control group (62.41% vs 12.89%, P < 0.0001). The risk of CTS was significantly higher in the ESRD on dialysis cohort (10-year cumulative incidence, 8.0%) than in the control cohort (5.1%), which yielded an adjusted hazard ratio of 13.95 (95% confidence interval, 10.95-17.76, P < 0.0001). The high risk of CTS in ESRD patients on dialysis suggests that timely referral to hand surgeons with appropriate treatment should prevent permanent median nerve damage by CTS and may possibly improve patients' quality of life.