OBJECTIVE This study aims to identify the most accurate method or ultrasonographic measurement for the diagnosis of carpal tunnel syndrome (CTS). METHODS Between October 2010 and April 2011, a total of 160 hands of 87 patients (4 males, 83 females; mean age 54.5 years; range, 26 to 84 years) with clinically and electrodiagnostically proven CTS and 80 hands of 40 controls (3 males, 37 females; mean age 53.7 years; range, 32 to 77 years) were evaluated by sonographic examination. The diameters and cross-sectional areas (CSA) of the median nerve and longitudinal diameters of the median nerve were measured at the inlet, proximal carpal tunnel, and outlet of the carpal tunnel. Volar bulging and thickness of the retinaculum were also measured. RESULTS The most optimal combination for the diagnosis of CTS was proximal CSA, volar bulging, and the proximal transverse diameter. The combination of proximal CSA with volar bulging increased the sensitivity and specificity of sonographic measurements. CONCLUSIONS Based on our study results, ultrasonography can be used as a practical modality to distinguish CTS patients from asymptomatic controls.