Because postoperative pain after total knee replacement (TKR) can be severe, we compared the analgesic efficacy of continuous femoral nerve blockade (CFNB) and continuous epidural analgesia (CEA) after TKR in this prospective randomized trial. Patients undergoing TKR under spinal anesthesia were randomized to receive either a femoral infusion of bupivacaine 0.2% (median infusion rate 9.3 mL/h) (n = 53) or an epidural infusion of ropivacaine 0.2% with fentanyl 4 microg/mL (median infusion rate 7.6 mL/h) (n = 55). Adjuvant analgesics were oral rofecoxib and oxycodone and IV morphine. Pain, nausea and vomiting, hypotensive episodes, motor block, range of knee movement, and rehabilitation milestones were assessed postoperatively. There were equivalent pain scores, range of movement, and rehabilitation in both groups. There was significantly less nausea and vomiting in the CFNB group (P < 0.002). The CFNB group received more rofecoxib (P < 0.04) and oxycodone (P < 0.005) than the CEA group. The operative limb displayed more motor block than the nonoperative limb in both groups at the level of the hip and knee for up to 48 h (P < 0.05, Mann-Whitney U-test), but there was no difference between groups in the nonoperative limb. CFNB is an effective regional component of a multimodal analgesic strategy after TKR.