INTRODUCTION: Therapeutic ultrasound has been suggested as a treatment for carpal tunnel syndrome (CTS), but existing trial evidence is of poor quality and inconclusive. METHODS: We conducted a randomized, controlled trial of therapeutic ultrasound in mild to moderate CTS. Forty patients were treated with wrist splints plus either real or sham therapeutic ultrasound and followed for 1 year posttreatment. The primary outcome was change in symptom severity scale score. Secondary outcomes were functional status scale score, nerve conduction studies, and ultrasound imaging of the median nerve. RESULTS: Both groups showed significant clinical and neurophysiological improvement at 6 and 12 months compared with baseline. There were no significant differences between groups at any time. In a multivariate analysis, the only independently significant predictors of the primary outcome were pretreatment symptom severity and additional treatments during follow-up. DISCUSSION: We found no clinically significant benefit from ultrasound treatment for CTS.