Recently, extracorporeal shock wave therapy (ESWT) has been shown to be a novel therapy for carpal tunnel syndrome (CTS). However, previous studies did not examine the diverse effects of different-session ESWT for different-grades CTS. Thus, we conducted a randomized, single-blind, placebo-controlled study. Sixty-nine patients (90 wrists) with mild to moderate CTS were randomized into 3 groups. Group A and C patients received one session of radial ESWT (rESWT) and sham eESWT per week for 3 consecutive weeks, respectively; Group B patients received a single session of rESWT. The night splint was also used in all patients. The primary outcome was Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) points, whereas secondary outcomes included the sensory nerve conduction velocity and cross-sectional area of the median nerve. Evaluations were performed at 4, 10, and 14 weeks after the first session of rESWT. Compared to the control group, the three-session rESWT group demonstrated significant BCTQ point reductions at least 14 weeks, and the effect was much longer lasting in patients with moderate CTS than mild CTS. In contrast, the effect of single-session rESWT showed insignificant comparison. rESWT is a valuable strategy for treating CTS and multiple-session rESWT has a clinically cumulative effect.