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Background: Although numerous methods of postoperative analgesia have been investigated in an attempt to improve pain control after total knee arthroplasty, parenteral narcotics still play a major role in postoperative pain management. Local anesthetics have the advantage of blocking pain conduction at its origin and minimizing the systemic side effects associated with postoperative narcotic use. This study was performed to evaluate the benefits and safety of a multimodal analgesia protocol that included periarticular injection of large doses of local anesthetics in patients undergoing total knee arthroplasty.Methods: We compared morphine consumption during the first twenty-four hours after unilateral total knee arthroplasty in forty-two patients who had been randomized to receive either (1) a perioperative infiltration mixture, consisting principally of local anesthetic, and self-administered morphine or (2) self-administered morphine only. Narcotics consumption, pain control, medication-related side effects, plasma levels of the local anesthetic (ropivacaine), and postoperative rehabilitation were monitored.Results: Although there was high satisfaction and good pain control in both groups, morphine consumption was significantly lower in the local analgesia group than it was in the control group (28.8 ± 17.4 mg compared with 50.3 ± 25.4 mg twenty-four hours after surgery, and 46.7 ± 19.4 mg compared with 68.6 ± 38.6 mg forty hours after surgery). Both groups achieved a similar amount of knee flexion on the fifth postoperative day. Over the five-day period after the procedure, the patients in the local analgesia group reported a total of 2.6 ± 3.9 hours of nausea compared with 7.1 ± 12.2 hours in the control group. No complications related to the infiltration of the local anesthetic were observed, and all plasma concentrations of the local anesthetic were below the toxic range.Conclusions: This multimodal perioperative analgesia protocol that included infiltration of a local anesthetic offered improved pain control and minimal side effects to patients undergoing total knee arthroplasty. Our study also confirmed the safety of the protocol.Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.