Introduction The aim of this study was to explore the acupuncture effect on the cross-sectional area (CSA) of the median nerve at the wrist in patients with carpal tunnel syndrome (CTS) and, additionally, to identify whether clinical, electrophysiological, and ultrasonographic changes show any association. Methods Forty-five limbs of 27 female patients were randomly divided into two groups (acupuncture and control). All patients used night wrist splint. The patients in the acupuncture group received additional acupuncture therapy. Visual analog scale (VAS), Duruöz Hand Index (DHI), Quick Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire scores, electrophysiologic measurements, and median nerve CSAs were noted before and after the treatment in both groups. Results VAS, DHI, Quick DASH scores, and electrophysiological measurements were improved in both groups. The median nerve CSA significantly decreased in the acupuncture group, whereas there was no change in the control group. Conclusion After acupuncture therapy, the patients with CTS might have both clinical and morphological improvement.