Two hundred forty-one patients undergoing primary total knee arthroplasty (TKA) were randomized to receive duloxetine 30 mg daily (n=126) or placebo (n=115), beginning one week prior to surgery and continuing for six weeks postoperatively. The outcomes of interest were postoperative opioid consumption measured in daily morphine milligram equivalents (MME), sleep duration, sleep quality, pain measured by visual analogue scale (VAS), and functional outcomes assessed by the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR). Outcomes were assessed during the first two postoperative weeks for opioid consumption and sleep metrics, and at six weeks for pain and functional outcomes. Overall, the results of the study revealed no significant differences between the duloxetine and placebo groups in opioid consumption, postoperative pain scores, sleep duration, or functional outcomes. However, patients receiving duloxetine reported improved subjective sleep quality. These findings suggest that duloxetine does not reduce opioid requirements or pain after TKA but may modestly improve perceived sleep quality during recovery.