Provided is a non-surgical method of treatment of carpal tunnel syndrome by administering an effective amount of purified collagenase I and II by injection onto a transverse carpal ligament, without penetrating the transverse carpal ligament. The purified collagenase I and II are obtained from Clostridium histolyticum, and the effective amount is a dose comprising a concentration of approximately 0.29 mg of the purified collagenase I and II to one ml diluent.