An in depth analysis of the reliability of ultrasonography to measure the cross-sectional area of the tibial nerve or any other peripheral nerve is not available in the literature. This study determined the reliability and size of the measurement error of high-resolution ultrasound to measure the size of the tibial nerve at the tarsal tunnel. The cross-sectional area of the tibial nerve was measured by two experienced sonographers at 1 cm proximal to the medial malleolus. Measurements were made in 10 healthy participants without plantar heel pain. Intra and intertester reliability were determined by calculation of intraclass correlation coefficients (ICC), measurement error magnitude and smallest detectable difference (SDD). A direct (tracing) and indirect (ellipsoid formula) method were evaluated. Results demonstrated that the intra and intertester reliability were excellent (ICC, all > or =0.86). The measurement error and SDD were very small, especially when measurements from three scans were averaged (measurement error: 0.4-0.9 mm2; SDD: 1.1-2.5 mm2). The findings of this study support the view that high-resolution ultrasound is reliable to measure the cross-sectional area of a peripheral nerve. As a result of the small measurement error, a side-to-side difference as small as approximately 1.8 mm2 can be interpreted meaningfully in an individual patient. This difference is much smaller than the swelling reported in the literature for patients with tibial neuropathy.