This prospective, double-blind randomized controlled trial included 120 patients undergoing total knee arthroplasty (TKA) to evaluate the efficacy of preemptive multimodal analgesia (PMA) administered at different time points before surgery. Patients were divided into three groups receiving PMA (200 mg celecoxib and 150 mg pregabalin) at either 48 hours (Group A), 24 hours (Group B), or 1 hour (Group C) before surgery. The primary outcome was postoperative morphine consumption, while secondary outcomes included time to first rescue analgesia, postoperative pain scores, functional recovery, hospital length of stay, and complication rates. Groups A and B exhibited significantly lower postoperative morphine consumption, longer time to first rescue analgesia, and improved knee range of motion on the first postoperative day compared to Group C, though no differences were found in pain scores, ambulation distance, length of hospital stay, or complications. These findings suggest that initiating PMA at 24 hours preoperatively is an effective option, though further research is needed to establish the optimal timing.