One hundred and six patients undergoing bilateral total knee arthroplasty (TKA) were randomized to receive either 20 mg of duloxetine (n=53) or a placebo (n=53) from preoperative day 2 to postoperative day 28. The primary outcome of interest was pain control, measured using the visual analogue scale (VAS) at rest (rVAS) and during mobilization (mVAS). Secondary outcomes included additional non-steroidal anti-inflammatory drug (NSAID) consumption, patient satisfaction, and safety profile assessment. Outcomes were assessed at 48 hours, 1 week, 2 weeks, 4 weeks, and 3 months postoperatively. Overall, the study revealed that duloxetine significantly reduced pain scores (rVAS and mVAS) and NSAID consumption during the first two postoperative weeks, with differences leveling off by the 4-week follow-up. Patient satisfaction was also higher in the duloxetine group, with a comparable safety profile. These findings suggest that duloxetine can be safely used for short-term pain relief in patients without central sensitivity undergoing bilateral TKA.