Objective: To compare the postoperative analgesic effect of modified superior trunk block and traditional interscalene brachial plexus block in arthroscopic rotator cuff repair. Methods: A total of 40 patients undergoing arthroscopic rotator cuff repair in the Second Affiliated Hospital of Wenzhou Medical University from October to November 2023 were prospectively included, whose American Society of Anesthesiologists (ASA) grade were Ⅰ-Ⅱ. They were divided into modified superior trunk block group (group S) and interscalene brachial plexus block group (group I) by random number table according to different nerve block methods, with 20 cases in each group. Local anesthetics was a mixture of 1.33% liposomal bupivacaine and 0.5% levobupivacaine hydrochloride injection in equal volume. Patients in group S were injected 5 ml mixture for ultrasound-guided modified superior trunk block, and patients in group I were injected with 15 ml mixture for ultrasound-guided traditional interscalene block respectively. Both groups underwent superficial cervical plexus block (5 ml mixture). Standardized general anesthesia and standardized postoperative analgesia were followed. The primary outcome measures included 48 h resting numerical rating scale (NRS) scores after surgery and the incidence of hemidiaphragmatic paralysis (HDP) at 30 min after block. The secondary outcome measures included resting NRS scores during the post anesthesia care unit (PACU), 12, 24, and 36 h after surgery, postoperative opioid consumption and satisfaction with analgesia, pulse oxygen saturation (SpO2) at 30 min after block, sensory and motor block duration, and the incidence of perioperative adverse reactions. The non-inferiority cut-off value of resting NRS scores for patients in group S was set as"1 point"at each observation time point after surgery. Results: In group S, one patient was excluded because the target nerve was blocked by the subclavian vein and could not be blocked, nineteen patients [11 males and 8 females, aged (52.2±9.0) years] were eventually included. In group I, there were 7 males and 13 females, aged (55.0±5.1) years. Resting NRS scores of group S and Group I at 48 h after surgery were 0 (0, 0) and 0 (0, 0.8) point, respectively, with no statistical significance (P>0.05). The median difference was 0 (95%CI:0-0) point and the upper 95%CI was 0 point, which was lower than the preset non-inferiority cut-off value"1 point"(non-inferiority P<0.001). The incidence of HDP in group S and group I were 5% (1/19) and 75% (15/20), respectively, with statistically significant (P<0.001). There were no significant differences in resting NRS scores at PACU and 12, 24, 36 h after surgery, opioid dosage, satisfaction with analgesia, SpO2 at 30 min after block, sensory and motor block duration between two groups (all P>0.05). No respiratory adverse events such as hypoxemia and airway spasm occurred in two groups after extubation. One patient in group I showed symptoms of breath shortness when entering PACU, and 3 patients felt uncomfortable due to prolonged numbness and weakness of the blockade limb (>2 days). No nerve block procedures and opioid drugs relative adverse reactions and no neurological complications happened in both groups. Conclusion: Liposomal bupivacaine usage for modified superior trunk block can provide long-term postoperative analgesic effects which is noninferior to traditional interscalene brachial plexus block and causes less HDP in patients undergoing arthroscopic rotator cuff repair.