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Background and Objectives: In this randomized double-blind prospective study in patients undergoing shoulder arthroscopy, we compared the effects of ultrasound-guided interscalene nerve block using 20 mL (intervention group) and 40 mL (control group) of a mepivacaine 1.5% and bupivacaine 0.5% mixture (1:1 volume) on ipsilateral handgrip strength and other postoperative end points., Methods: One hundred fifty-four patients scheduled for ambulatory shoulder arthroscopy were randomly assigned to receive a single-injection interscalene block under ultrasound guidance with either 40 mL (control) or 20 mL (intervention) and intravenous sedation. The primary outcome was the change in ipsilateral handgrip strength in the postanesthesia care unit (PACU) measured with a dynamometer. Secondary end points were recorded, including negative inspiratory force, incidences of hoarseness and Horner syndrome, time to readiness for discharge from PACU, time to discharge from PACU, patient satisfaction, time to block resolution, and pain scores., Results: Postoperative handgrip strength was greater in the 20-mL group compared with the 40-mL group (difference in means, 2.3 kg [95% confidence interval, 0.6-4.0 kg]; P = 0.009). A smaller proportion of patients in the intervention group experienced hoarseness postoperatively compared with the control group (odds ratio, 0.26 [95% confidence interval, 0.08-0.82]; P = 0.015). Patient satisfaction and duration of analgesia were similar in both groups., Conclusions: When used for surgical anesthesia for shoulder arthroscopies in the ambulatory setting, a 20-mL volume in an ultrasound-guided interscalene block preserves greater handgrip strength on the ipsilateral side in the PACU compared with 40 mL without significant decrease in block success, duration of analgesia, and patient satisfaction.