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ABSTRACT Introduction We assessed the yield of high-resolution ultrasonography (HRUS) in patients with clinically definite carpal tunnel syndrome (CTS) and normal nerve conduction studies (NCS). Methods This blinded, prospective, cross-sectional study involved 35 patients (60 hands) with clinically definite CTS and normal NCS, and 20 controls (40 hands). Cross-sectional area (CSAs) of the median nerve at the level of the pisiform bone and flexor retinaculum thickness (FRT) were measured. Results CSA was abnormal in 48.6% of patients (confidence interval 32.0-65.2%, P = 0.95). FRT was increased in only 34.3% (18.3-49.7%), but was independently abnormal in 2 patients. CSA abnormalities correlated with positive provocative tests and sensory loss. The HRUS changes were mild. Conclusions HRUS confirms clinically diagnosed CTS in about half of the patients with normal NCS. Muscle Nerve 51: 592-597, 2015 [ABSTRACT FROM AUTHOR]