PURPOSE: To test the hypothesis that division of muscle fibers lying over or within the transverse carpal ligament (TCL) in an open carpal tunnel release does not have an effect on outcomes in patients with carpal tunnel syndrome (CTS). METHODS: A total of 152 patients with a mean age of 57 years (range, 31-83 years) diagnosed with CTS were enrolled for intraoperative observation of the muscles overlying or within the TCL as seen through a 3-cm incision. These muscles when present were incised layer by layer in line with division of the TCL. Patients were divided into 3 groups according to the extent of the muscles covering the TCL. We compared the 3 groups for outcomes of surgery at 6 months in terms of the Boston and Disability of Arm, Shoulder, and Hand (DASH) scores, grip and pinch powers, and scar pain. RESULTS: Of the 152 patients, 75 had a purely ligamentous TCL (group 1), 52 had muscle fibers covering 50% or less of the incision length (group 2), and 25 had muscle fibers covering more than 50% of the incision length (group 3). There were no differences in the postoperative Boston symptom and function scores and the DASH scores among the groups. In addition, there were no differences in the grip and pinch strengths and scar pain. CONCLUSIONS: Division of the muscles overlying or within the TCL in line with the third web space incision does not affect postoperative outcomes after carpal tunnel release in terms of the Boston and DASH scores, grip and pinch powers, and scar pain. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic I.