BACKGROUNDMultimodal analgesia is central to pain management after total knee arthroplasty (TKA). This study aimed to evaluate the efficacy of adding oral nefopam to multimodal analgesia for post-TKA pain management.METHODSIn this prospective, double-blind, placebo-controlled, randomized trial, 100 patients who underwent TKA at our hospital were randomized to either the nefopam or the control group. After surgery, patients in the nefopam group received 200 mg of celecoxib, 150 mg of pregabalin, and 40 mg of nefopam twice daily to control postoperative pain. Patients in the control group received 200 mg of celecoxib, 150 mg of pregabalin, and a placebo. Oxycodone hydrochloride (10 mg) was used as the rescue analgesic. If the pain remained poorly controlled, 10 mg of morphine hydrochloride was injected subcutaneously as a secondary rescue analgesic. The primary outcome was the postoperative consumption of oxycodone and morphine as rescue analgesics. Secondary outcomes were postoperative pain assessed using the visual analogue scale (VAS), functional recovery assessed by the range of knee motion and ambulation distance, time until hospital discharge, indicators of liver function, and complication rates.RESULTSPatients in the nefopam group had significantly lower postoperative oxycodone and morphine consumption within 24 hours after surgery and during hospitalization, lower VAS pain scores at rest and during motion within 24 h after surgery, better functional recovery on postoperative days 1 and 2, and a shorter hospital stay. However, the absolute reduction in 0 to 24 h opioid consumption, VAS pain scores, and knee range of motion did not exceed the reported minimal clinically important difference. Both groups had similar indicators of liver function and complication rates.CONCLUSIONSAdding oral nefopam to multimodal analgesia resulted in statistically significant improvements in opioid consumption, VAS pain scores, and functional recovery. However, the amount of improvement may not be clinically important.