Ninety patients scheduled for total knee arthroplasty were randomized to receive an infiltration between the popliteal artery and capsule of the knee (iPACK) block plus adductor canal block (ACB) (n=30), an L2 lumbar erector spinae plane block (L-ESPB) (n=30), or no regional block (control) (n=30). The primary outcome was total opioid consumption within 48 hours. Secondary outcomes included pain scores at predefined postoperative intervals, time to first rescue opioid, quadriceps strength, and inflammatory markers (NLR, PLR). Outcomes were assessed up to 48 hours. Overall, the results of the study revealed that iPACK+ACB produced the lowest opioid consumption and the longest time to first rescue analgesia, outperforming both ESPB and control. ESPB was moderately effective but less potent than iPACK+ACB. These findings suggest that iPACK+ACB remains the most effective analgesic regional anesthesia strategy for TKA among the techniques evaluated.