One hundred thirty-five patients undergoing primary 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 in Morphine Milligram Equivalents (MME) over a two-week period. Secondary outcomes included daily MME use from postoperative day (POD) 0 to POD4 and pain scores assessed via Visual Analog Scale (VAS). Outcomes were tracked continuously for two weeks. Overall, the methadone group demonstrated significantly lower daily MME use from POD0 to POD4 (e.g., POD0: 19.5 vs. 26.3; p=0.005), although the total two-week MME difference was not statistically significant (268.6 vs. 310.9; p=0.225). Pain scores were similar between groups, except on POD1 (p=0.027). These findings suggest preoperative methadone reduces early postoperative opioid use, warranting further study on optimal dosing and long-term risks.