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Background and objectives Ultrasound-guided axillary block (USGAB) is currently an accepted anesthesia technique for surgery of the hand, wrist or elbow. Recently, a new strategy for upper extremity surgery has emerged—Wide-Awake Local Anesthesia, No Tourniquet (WALANT). This prospective, randomized, single-center, double-blind, non-inferiority trial compared WALANT versus USGAB to provide surgical anesthesia in outpatient endoscopic carpal tunnel release (CTR).Methods Patients undergoing endoscopic CTR (n=130) were randomly allocated to WALANT or USGAB using lidocaine. The primary outcome was the success rate of WALANT versus USGAB in providing surgical anesthesia. A successful block was defined as adequate anesthesia for surgery without the need for supplementation.Results The proportion of subjects who achieved a successful block was 89% in the USGAB group versus 100% in the WALANT group. Non-inferiority of WALANT with respect to USGAB was confirmed (p<0.05). Postoperative function was similar in both groups except for the ability to dress, which was improved in the WALANT group compared with the USGAB group (92% vs 58%; p<0.001). No statistical differences regarding regional anesthesia satisfaction scores were observed except that the discomfort elements were improved in the WALANT group (p<0.05). Surgical assessment of intraoperative bleeding was similar in both groups (p=0.37).Conclusions For outpatient endoscopic CTR, the success rate of WALANT technique is non-inferior to USGAB.Trial registration number NCT06040840.