Background: The present, open-labeled study aimed to compare the distal approach (DA) for local corticosteroid injection (LCI) with the conventional proximal approach (PA) in alleviating the symptom and improving the electrodiagnostic parameters of the patients with carpal tunnel syndrome (CTS). Methods: A total of 60 participants with nonsevere CTS were included in the present randomized controlled trial (RCT), of which 29 and 31 were assigned to the DA and PA groups, respectively. Each group received a single, landmark-guided injection of local methylprednisolone. The participants were assessed preintervention and 3 months later using the measures of visual analog scale (VAS), Boston Carpal Tunnel Questionnaire (BCTQ), hand grip strength, and nerve conduction study (NCS). Results: Following a 3-month follow-up, both groups had significant improvements in VAS, both functional and severity subscales of BCTQ, hand grip strength, and some electrodiagnostic parameters (all P-values < .05). Moreover, the DA group had a significantly lower procedure duration than the PA group (9.80 ± 1.12 vs. 27.61 ± 1.77; P < .001). Conclusions: LCI using the DA should be considered a feasible, safe, and effective therapeutic method in patients with mild to moderate CTS. It had a shorter procedure duration than conventional PA, while their clinical and electrophysiological results were similar.