Background & objective: Brachial plexus block (BPB) is a widely utilized regional anesthesia technique for upper limb surgeries, known for its targeted action and ability to reduce the need for general anesthesia. However, predicting its success remains a clinical challenge due to variability in onset times. Reliable predictors such as changes in the perfusion index (PI) and skin temperature (ST) could enable earlier and more accurate identification of successful blocks, thereby preventing unnecessary interventions. This study aimed to compare the diagnostic accuracy of PI and ST in predicting BPB success. Methods: In this prospective, comparative study conducted between November 2020 and July 2022, 100 patients undergoing elective upper limb surgeries under ultrasound-guided BPB were enrolled at Aarupadaiveedu Medical College, Puducherry, India. PI was measured using a pulse oximeter, and ST was recorded using an infrared thermometer at baseline and at 5, 10, 15, and 20 minutes after block administration. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy, was evaluated for both PI and ST. Results: The mean time for a successful BPB was 14.5 minutes. PI changes were statistically significant as early as 5 minutes post-block, whereas ST changes became significant only after 10 minutes. At 15 and 20 minutes, PI demonstrated superior diagnostic accuracy, reaching 82% and 98%, respectively, compared to 39% and 62% for ST. At 20 minutes, PI achieved 100% sensitivity, 66.7% specificity, 97.9% PPV, and 100% NPV. In contrast, ST at 20 minutes showed 63.8% sensitivity, 33.3% specificity, 93.8% PPV, and 5.6% NPV. Conclusions: Perfusion index is a more reliable and earlier indicator of BPB success compared to skin temperature. PI changes were evident as early as 5 minutes post-block, making it a valuable non-invasive tool for real-time evaluation of block efficacy. Incorporating PI monitoring into routine clinical practice can facilitate timely interventions and improve patient outcomes.