Proponents of endoscopic carpal tunnel release claim less pain and scar tenderness, quicker recovery of strength, and earlier return to work and daily activities over open methods to release the transverse carpal ligament. This single-center prospective study is the first to compare three different treatment methods: standard open release, a single-portal endoscopic technique (Agee), and a two-portal endoscopic technique (Chow). Two hundred eleven releases in 163 patients were evaluated by clinical outcomes questionnaire and objective testing over a 6-month follow-up period. There was no difference in resolution of paresthesias or nocturnal pain between treatment methods. Patients treated with open release reported more thumb weakness and pain with activities of daily living after surgery. Endoscopically treated patients achieved faster recovery of grip and pinch strength and wrist range of motion. Patients treated endoscopically had less mid-palm tenderness than did patients treated via the open technique, and Agee patients had less distal palmar tenderness than did patients treated via other methods. Overall, and in the workers' compensation group, patients treated endoscopically returned to work sooner. In the non-workers' compensation group, Agree patients returned to work sooner than did patients treated via the other two methods.