One hundred thirty-five patients undergoing total knee arthroplasty (TKA) were randomized to receive either a single preoperative dose of methadone (10 mg; n=67) or oxycodone (10 mg; n=68). The primary outcome was postoperative opioid consumption, measured as daily Morphine Milligram Equivalents (MME) over two weeks. Secondary outcomes included daily pain scores assessed via the Visual Analog Scale (VAS). Outcomes were measured from postoperative day (POD) 0 to POD 14. Overall, the methadone group showed significantly reduced daily opioid consumption from POD 0 to POD 4 (e.g., POD 0: 19.5 vs. 26.3 MME, p=0.005). However, the total two-week opioid consumption and VAS pain scores, except for POD 1, were not significantly different. These findings suggest that methadone effectively reduces short-term postoperative opioid use compared to oxycodone.