Background: To compare the clinical effectiveness of ultrasound-guided corticosteroid injection with and without needle release of the transverse carpal ligament (TCL) in carpal tunnel syndrome (CTS). Methods: Between May 2014 and June 2016, 52 patients (56 wrists) with CTS were included in this study. Among these patients, 28 wrists were treated with ultrasound-guided corticosteroid injection plus needle release of the TCL (group A) and 28 wrists were treated with a single ultrasound-guided corticosteroids injection (group B). The following parameters were assessed and compared including postoperative results of procedure based on relief of symptoms, electrophysiological parameters (distal motor latency, sensory conduction velocity, and sensory nerve action potential of median nerve), and ultrasound parameters (anteroposterior diameter and cross-sectional area of the median nerve at the levels of pisiform and hamate bone, and the thicknesses of TCL on the cross-section at the level of hamate bone). Results: The overall excellent and good rate regarding the postoperative results of procedure based on the relief of symptoms at 1 month postoperatively was 82.1% in group A and 46.4% in group B (p = 0.004). There was significant difference in the above electrophysiological and ultrasound parameters between the preoperative and postoperative values in both groups (all p < 0.05). Furthermore, a significant difference was also observed in the postoperative values of the above-mentioned electrophysiological and ultrasound parameters in the 2 groups (all p < 0.05). Conclusions: Both approaches had treatment benefit in CTS. Ultrasound-guided corticosteroid injection in combination with needle release of the TCL is superior to the single ultrasound-guided corticosteroids injection.