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Background and Aims Ultrasound-guided brachial plexus block (USG-BPB) is widely used in upper limb surgery but may fail in up to 12.9% of cases. Identifying contributing factors remains a clinical challenge. This study aimed to identify predictors of USG-BPB failure to improve clinical outcomes.Methods A retrospective cohort study was conducted in patients undergoing upper limb surgery with USG-BPB at a university hospital between 2019 and 2023. Block failure was defined as the need for supplemental blocks, multiple doses or types of analgesics or sedatives, deep sedation (propofol>100 mcg/kg/min), or conversion to general anesthesia. Patient demographics, procedural details, and surgical variables were recorded. Univariate analysis was performed, followed by multivariate logistic regression including variables with p<0.1 and clinical relevance. Adjusted odds ratios (OR) were calculated, with p<0.05 considered statistically significant. This study was approved by the Institutional Ethics Committee (REC-67–249-8–4), on 11 June 2024.Results Of 657 cases reviewed, 606 were included in the final analysis. Block failure occurred in 112 cases (22.67%). Significant predictors included liver disease (OR=5.11, p=0.025), surgical duration ≥120 minutes (OR=3.44, p< 0.001), block-to-incision delay >30 minutes (OR=1.75, p=0.018), and use of single-agent local anesthetics—lidocaine (OR=3.06) or bupivacaine (OR=2.94) compared to mixed solutions (p=0.011). First- and second-year residents had the highest failure risk (OR=6.19, p<0.001). Protective factors included hand surgery (OR=0.35, p=0.023), diabetes mellitus (OR=0.42, p=0.003), and higher block volume (OR=0.93, p=0.011).Conclusions Failure of USG-BPB is associated with operator inexperience, liver disease, prolonged surgical time, delayed incision, and the use of single-agent local anesthetics,while diabetes, hand surgery, and higher block volume are protective. Optimizing operator training, anesthetic technique, and timing may improve block success.Abstract EP123 Table 1Multivariate logistic regression analysis of factors associated with failure of ultrasound-guided brachial plexus block (USG-BPB). Adjusted odds ratios (OR), 95% confidence intervals (CI), and p-values are presented for each variable. Significant predictors of block failure include liver disease, operator inexperience (particularly first- and second-year residents), use of single-agent local anesthetics (lidocaine or bupivacaine), prolonged surgery (>120 minutes), delayed time from block to incision (>30 minutes).Protective factors include diabetes mellitus, hand surgery and higher block volume.