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Background: To investigate if combined single-shot adductor canal blockade (ACB) and infiltration between the popliteal artery and capsule of the knee (IPACK) provide better postoperative pain management compared to ACB alone for patients undergoing unilateral total knee arthroplasty (TKA). Methods: This retrospective cohort study included adult patients who underwent primary, unilateral TKA. Patients were separated into 2 cohorts: single-shot ACB alone (performed with bupivacaine 0.25%) and combined single-shot ACB + IPACK (performed with bupivacaine 0.25%, dexmedetomidine 1 mg/kg, and dexamethasone 4 mg). Patients were propensity-matched 1:1. The primary study outcome was total opioid consumption converted to morphine milligram equivalents (MME) per eight-hour interval and postoperative day. Secondary outcomes included pain scores, length of stay, ambulation distance, return to emergency department, hospital readmission, and 30-day adverse events. Results: One hundred eighty patients were identified, of which propensity matching used 71% to yield 64 patients receiving ACB alone and 64 receiving combined ACB + IPACK. Combined ACB + IPACK had significantly lower total summative MME throughout the entire postoperative stay (P = .002) and cumulatively after the first 24 hours (P < .001). Combined ACB + IPACK also had lower mean pain scores for 0-8 hours (P = .005) and 8-16 hours (P = .009) postoperatively. There were no significant differences in secondary outcomes. Conclusions: Combined single-shot ACB + IPACK block was associated with lower total narcotic intake and mean pain scores during most of the immediate postoperative period following primary, unilateral TKA compared to ACB alone. Implementing longer-acting, single-shot ACB + IPACK for TKA can balance effective and more selective pain management with early rehabilitation.