The relative analgesic efficacy and side-effect profile of peripheral nerve blockade (PNB) techniques compared with lumbar epidural analgesia for major knee surgery is unclear. We undertook a systematic review and meta-analysis of all randomized trials comparing epidural analgesia with PNB for major knee surgery. Eight studies were identified that had enrolled a total of 510 patients of whom 464 (91%) had undergone total knee joint replacement. All were small trials and none was blinded (Jadad score 1-3). PNB technique was variable: in addition to a femoral catheter (n=5), femoral single shot (n=2), or lumbar plexus catheter (n=1) techniques, sciatic blockade was performed in three trials. There was no significant difference in pain scores between epidural and PNB at 0-12 or 12-24 h, WMD 0.22 (95% CI: -0.36, 0.81), 0.05 (-1.01, 0.91), respectively, and no clinically significant difference at 24-48 h, WMD -0.35 (-0.64, -0.02). There was also no difference in morphine consumption (mg) at 0-24 h, WMD -6.25 (-18.35, 5.86). Hypotension occurred more frequently among patients who received epidurals [OR 0.19 (0.08, 0.45)], but there was no difference in the incidence of nausea and vomiting. Two studies reported a higher incidence of urinary retention in the epidural group. Patient satisfaction was higher with PNB in two of three studies which measured this, although rehabilitation indices were similar. PNB with a femoral nerve block provides postoperative analgesia which is comparable with that obtained with an epidural technique but with an improved side-effect profile and is less likely to cause a severe neuraxial complication.