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Peroneal nerve palsy is a rare complication of total knee arthroplasty (TKA). Previous studies have investigated surgical variables contributing to the development of peroneal nerve palsy after TKA, but have ignored potential medical and anesthetic risk factors. The charts of all patients undergoing TKA over a 1-yr period were retrospectively studied to identify medical, surgical, and anesthetic risk factors contributing to the development of peroneal nerve palsy after TKA; 361 TKAs were performed on 292 patients. There were eight peroneal nerve palsies in seven patients representing an overall incidence of 2.2%. A preoperative valgus deformity ≤l0°, total tourniquet time >120 min, the diagnosis of a preexisting neuropathy, and postoperative bleeding complications were identified as significant risk factors. Postoperative epidural analgesia was used in 108 cases and was not a significant risk factor for the development of peroneal palsy. However, all cases of peroneal nerve palsy with motor deficits and partial neurologic recovery occurred in patients receiving postoperative epidural analgesia and were diagnosed after discontinuation of the epidural infusion. Since diagnosis of peroneal nerve palsy may be delayed in patients with postoperative epidural analgesia, these patients must be monitored closely. A dilute local anesthetic or an opioid infusion is recommended for patients at increased risk, such as those with preexisting neuropathies.