Objective To investigate the clinical effect of steroid in the treatment of patients with carpal tunnel syndrome (CTS) using clinical scores and neurosonology.Methods A total of 42 patients with CTS who met the inclusion criteria were enrolled consecutively from August 2015 to July 2016 and divided according to the number of enrollment. The 22 patients with odd numbers were given oral steroid (oral group) and the 20 patients with even numbers were given local injection of steroid (injection group). The degree of electrophysiological abnormalities was classified as mild, moderate, severe, or extremely severe for all patients before treatment. Determination of clinical scores and high-frequency ultrasound examination were performed before treatment and at 1 month after treatment. The clinical scores included the CTS Global Symptom Score (GSS), Boston Symptom Severity Scale (SSS), and Functional Status Scale (FSS). High-frequency ultrasound transverse scan was performed to measure the cross-sectional area (CSA) of the median nerve, including the carpal tunnel entrance, central carpal tunnel, carpal tunnel exit, and forearm (CSA1, CSA2, CSA3, and CSA4, respectively), and longitudinal scan was performed to measure the diameters of the finest and largest sections (D1 and D2, respectively). The differences (Δ) and rates (R) of the parameters before and after the treatment were calculated.Results After the treatment, both groups had significant reductions in the clinical scores of GSS, SSS, and FSS and the ultrasound parameters CSA1, CSA2, CSA3, D, and R-CSA (P<0.05). The injection group had significantly higher ΔCSA1 and ΔR-CSA than the oral group (P<0.05). In the patients with mild and moderate CTS, the injection group had significantly higher ΔCSA1 and ΔR-CSA than the oral group (P<0.05), while in patients with severe and extremely severe CTS, there were no significant differences in these parameters between the two groups (P>0.05).Conclusions In patients with mild and moderate CTS, local injection of steroid at the carpal tunnel has a better short-term clinical effect than oral administration. Neurosonological evaluation has clinical significance in evaluating the clinical effect, and a combination of ΔCSA1 and ΔR-CSA can better assess the clinical effect.