OBJECTIVE The few papers published on the use of sonography in carpal tunnel syndrome suggest it may be a useful diagnostic test. This study aims to prospectively evaluate the use of sonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome. METHODS Patients with documented carpal tunnel syndrome and a group of asymptomatic control subjects were enrolled and underwent high-resolution sonography of the carpal tunnel. A small-footprint linear array transducer was used to scan and measure the median nerve cross-sectional area and the maximum transverse and anteroposterior diameters. Data from the patient group and the control group were compared to establish optimal diagnostic criteria for carpal tunnel syndrome. RESULTS Sixty-eight carpal tunnel syndrome patients (50 women, 18 men) with 102 affected nerves and 68 nerves in 36 asymptomatic controls (23 women, 13 men) were examined. Qualitative assessment alone was found to be unreliable. All measurements showed significant differences between patients and controls. The most predictive measurement was swelling of the median nerve, which was significantly greater in carpal tunnel syndrome patients compared with controls (mean, 0.13 cm2 versus 0.07 cm2). Thus, quantitative assessment of the median nerve provides an accurate diagnostic test (sensitivity, 82%; specificity, 97%), with an area larger than 0.09 cm2 being highly predictive of carpal tunnel syndrome. CONCLUSIONS We confirm that median nerve cross-sectional area measurement correlates well with the presence of carpal tunnel syndrome and is both sensitive and specific for the diagnosis.