Background: The most common entrapment mononeuropathy of the upper extremity is carpal tunnel syndrome (CTS). It consists 90% of entrapment neuropathies. The purpose of this study was to compare cross-sectional area (CSA) of the median nerve at the wrist in CTS patients and healthy controls and define the best cut-off point of CSA to differentiate patients and controls in Iranian population.Methods: In this study, 45 patients with confirmed idiopathic CTS and 62 healthy controls were evaluated. Based on electrophysiological findings, patients were divided based on CTS severity into three groups of mild, moderate and severe. The largest CSA was measured at the level of distal wrist crease which is consistent with carpal tunnel inlet.Results: Mean CSA was 0.124 ± 0.031 mm2, 0.146 ± 0.028 mm2 and 0.194 ± 0.062 mm2 in mild, moderate and severe CTS patients respectively, and 0.077 ± 0.011 mm2 in controls. Our results showed that participants with CSA > 0.010 had CTS with 100% specificity and 83.12% sensitivity.Conclusion: It is possible to diagnose CTS by measuring CSA and using above-mentioned cut-off point.