Background: Major shoulder surgery is associated with moderate-to-severe pain, but consensus on the optimal analgesic approach is lacking. Continuous catheter-based interscalene block (CISB) prolongs the analgesic benefits of its single-injection counterpart (SISB), but concerns over CISB complications and difficulties in interpreting comparative evidence examining major and minor shoulder procedures simultaneously, despite their differences in postoperative pain, have limited CISB popularity. This meta-analysis evaluates the CISB analgesic role and complications compared with SISB for major shoulder surgery.Methods: We retrieved randomised controlled trials (RCTs) comparing the effects of CISB to SISB on analgesic outcomes and side-effects after major shoulder surgery. Postoperative opioid consumption at 24 h was designated as the primary outcome. Secondary outcomes included 24-48 h opioid consumption, postoperative rest and dynamic pain scores up to 72 h, time-to-first analgesic, recovery room and hospital stay durations, patient satisfaction, postoperative nausea and vomiting, respiratory function, and block-related complications.Results: Data from 15 RCTs were pooled using random-effects modelling. Compared with SISB, CISB reduced 24-and 48-h oral morphine consumption by a weighted mean difference [95% confidenceinterval] of 50.9 mg[-81.6, -20.2], (P = 0.001) and 44.7 mg[-80.9,-8.7], (P<0.0001), respectively. Additionally, CISB provided superior rest and dynamic pain control beyond 48 h, prolonged time-to-first analgesic, enhanced satisfaction, and reduced postoperative nausea and vomiting without complications. CISB caused an 11.0-11.7% decrease in respiratory indices. Result heterogeneity was successfully explained.Conclusions: High-level evidence indicates that CISB provides superior analgesia up to 48 h after major shoulder surgery, without increasing side-effects, compared with SISB. The importance of CISB-related changes in respiratory indices is questionable.