Objective To examine the value of ultrasound (US) in the diagnosis of carpal tunnel syndrome (CTS) in the Vietnamese population. Methods This prospective cross-sectional study involved 42 wrists of 25 patients with idiopathic CTS evaluated by US. In addition, 38 wrists of 22 healthy volunteers were included as the control group. Results Significant differences in the median nerve cross-sectional area (CSA) at different levels were found between patients with CTS and controls. Using a cut-off value of 9.5 mm2 for the median nerve CSA at the pisiform (p-CSA), US had a sensitivity and specificity of 95.2% and 97.4%, respectively, for the diagnosis of CTS. Area under the curve analysis revealed a sensitivity and specificity of 100% and 95.4%, respectively, for the prediction of severe CTS using a p-CSA of >15.5 mm2. Conclusions The median nerve CSA is a highly accurate parameter in the diagnosis of CTS. We recommend using a p-CSA of >9.5 mm2 as a diagnostic criterion for CTS and a p-CSA of >15.5 mm2 as a marker for severe CTS in the Vietnamese population. Research Registry number: 7261