This study compares results of endoscopic carpal tunnel release using the two-portal technique in two groups of patients based on whether or not they were receiving workers' compensation. There were 50 patients in the worker's compensation group and 63 in the nonworker's compensation group. Mean follow-up was 40.8 months and 44.8 months, respectively. Duration of symptoms before surgery was statistically different in the two groups, 13.6 months in the worker's compensation groups compared to 26.2 months in the nonworker's compensation group. Worker's compensation patients tended to be younger, have shorter duration of symptoms before surgery, report lower postoperative activity levels, have more subsequent surgeries, and have mediocre results when compared to nonworker's compensation patients. There was no statistically significant difference in the rate or timing of return to work. Our series of 113 patients who had endoscopic carpal tunnel release indicates that careful patient selection is necessary to achieve satisfactory outcomes in worker's compensation patients.