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Objective: To evaluate the accuracy and utility of ultrasonography for the diagnosis of carpal tunnel syndrome (CTS). Material and method: Prospective and blind study of 75 wrists in 42 consecutive patients with suspected CTS. Electrodiagnostic testing (EDT) was used as gold standard. We measure different ultrasonographic parameters and based on a fitted receiver operating characteristic curve, we estimated post-test probabilities for the proximal, middle and distal cross-sectional area of median nerve. We analyzed interobserver and interreader reliability by 3 different explorers and 2 different readers, cost and the patient discomfort. Results: Mean ultrasound measurements were significantly higher in the EDT positive group. There was a high concordance between sonography and nerve conduction. A cut-off of 9.5 mm² resulted in the correct classification of 83% of cases (sensitivity 88% and specificity 67%). Conversely, a cut-off of > 14 mm² or <7 mm² had excellent power to rule in CTS, with a post-test probability of 100% of specificity and sensitivity respectively. The interobserver acquisition ICC was 0.915-0.980, and the inter-reader ICC was 0.912-0.987. Ultrasound cost savings in this study were €33217.59 (€42.9 per symptomatic wrist) and the discomfort perceived by the patient was significantly lesser 6.3 vs 56 in EDT (P<.0005). Conclusions: Ultrasound median nerve cross-sectional area is reliable and may be used to accurately rule in or rule out CTS, Sonography as a first-line test is cost-effective and is more satisfactory to the patients. [ABSTRACT FROM AUTHOR]