Background <p>Although interscalene nerve block is considered as the standard analgesic method for arthroscopic shoulder surgery, it is not indicated for patients with respiratory comorbidity. Periarticular infiltration is usually used for postoperative analgesia following orthopedic surgery, with uncertain analgesic effects. Infraspinatus-teres minor interfascial (ITM) block is an innovative method used in arthroscopic shoulder surgery. We supposed that ITM block combined with periarticular infiltration could provide adequate analgesia for patients undergoing arthroscopic shoulder surgery.</p> Methods <p>This is a randomized, parallel-controlled, prospective, single-center study. Fifty-six patients scheduled for arthroscopic shoulder surgery will be randomized into two groups: ITM block combined with periarticular infiltration group (ITM group) and periarticular infiltration group (PAI group). Periarticular infiltration will be administered to all patients following surgery. The primary outcome is the time from the end of surgery to the first press of the patient-controlled analgesia pump (PCA) in the two groups. Secondary outcomes are the following: intraoperative remifentanil and propofol consumption, hemodynamic changes, VAS scores, frequency of PCA compression, remedy analgesic consumption, length of hospital stay, patients satisfaction score, and adverse reactions.</p> Discussion <p>This study will demonstrate the analgesic efficacy of ITM block combined with periarticular infiltration in arthroscopic shoulder surgery.</p> Trial registration <p>Chinese Clinical Trial Registry (<a href="https://www.chictr.org.cn/">https://www.chictr.org.cn/</a>) ChiCTR2400088821. Registered on 27 August 2024.</p>