Background: To evaluate the efficiency of the percutaneous 18-G needle technique in releasing the fibro-osseous sheath over the first dorsal extensor compartment of the hand. Methods: Using anatomic landmarks, percutaneous release was performed with an 18-G needle on 48 wrists of 24 cadavers. The specimens were then dissected and examined for the completeness of the first dorsal extensor compartment release and any tendon or neurovascular injuries. The tunnel length, number of abductor pollicis longus and extensor pollicis brevis tendons, presence of an intertendinous septum, and the effects of these parameters on percutaneous release were evaluated. Results: Percutaneous release was performed on all of the wrists, and the evaluation of the adequacy of release revealed 25 complete releases, 21 partial releases, and 2 missed releases. There were 19 cases of tendon complications. No neurovascular injuries were noted. The mean tunnel length was 2.66 ± 30 cm, and the mean number of tendons was 2.75 ± 0.86. A septum was present in 33.3% of cases. Tunnel length and tendon number had no statistically significant effect on release, whereas the presence of a septum was significantly associated with inadequate tunnel release and the development of tendon complications. Conclusions: Percutaneous release of the first dorsal extensor compartment using an 18-G needle was associated with high rates of incomplete release and tendon damage in the presence of an intertendinous septum. Further study is required under ultrasound guidance to determine the usefulness of percutaneous release in the first dorsal extensor compartment. Clinical Relevance: Release with a percutaneous needle tip in De Quervain’s syndrome may provide the advantages of better cosmetic results with less scar formation and an early return to work.