In prior studies, epidural analgesia and femoral nerve blockade have separately demonstrated improved pain relief, lower narcotic consumption, and enhanced rehabilitation outcomes following total knee arthroplasty (TKA). No studies to date have addressed the effectiveness of combining femoral nerve blockade with epidural analgesia. This study investigated whether further benefits could be obtained by combining a single-injection femoral nerve blockade with epidural analgesia. Eighty patients of a single surgeon who were undergoing routine primary TKA for osteoarthritis were enrolled in an institutional review board-approved, prospective, randomized, controlled, and blinded study. The patients consented to enrollment prior to surgery and were randomized into a femoral nerve block group and a no block group. Both groups received a combined spinal-epidural anesthetic and patient-controlled epidural analgesia with 0.06% bupivacaine and 10 [mu]g/mL hydromorphone. In addition, the block group of 41 patients received a femoral nerve block with 0.375% bupivacaine/5 [mu]g/mL epinephrine prior to surgery and epidural placement. All patients received the same, standardized physical therapy intervention. Clinicians who were blinded to group assignment conducted postoperative pain management, rehabilitation, and data analysis. Both groups were well matched in terms of demographics. There were no complications associated with the administration of the femoral nerve block or combined spinal-epidural anesthesia. The incidence of side effects was not significantly different between the groups. Patients who received a femoral nerve block had significantly lower visual analogue scale pain scores in the recovery room through postoperative day 3. Patients who received a femoral nerve block also required significantly less epidural medication. Patients who received a femoral nerve block had a significant improvement in flexion range of motion and CPM flexion on postoperative day 2. Although a consistent trend favored the block group for other physical therapy outcomes including ambulation distance, independent transfer, use of a walker, and progression to a cane, statistical significance was not achieved. The addition of a single-injection femoral nerve block to epidural analgesia significantly improved pain control for the first 3 days following TKA. No increased rate of side effects was observed. Improvements in physical therapy outcomes were noted. Femoral nerve block and epidural analgesia have become the standard therapy at the Hospital for Special Surgery after TKA.