To examine the interaction of epidural anesthesia, coagulation status, and outcome after lower extremity revascularization, 80 patients with atherosclerotic vascular disease were prospectively randomized to receive general anesthesia combined with postoperative epidural analgesia (GEN-EPI) or general anesthesia with on-demand narcotic analgesia (GEN). Demographics did not differ between groups except that the GEN-EPI group had a higher incidence of diabetes mellitus and of previous myocardial infarction. Coagulation status was monitored using thromboelastography. An additional 40 randomly selected patients without atherosclerotic vascular disease undergoing noncardiovascular procedures served as controls for coagulation status. Vascular surgical patients were hypercoagulable compared with control patients before operation and on the first postoperative day. Postoperatively, this hypercoagulability was attenuated in the GEN-EPI group and was associated with a lower incidence of thrombotic events (peripheral arterial graft coronary artery or deep vein thromboses). The rates of cardiovascular, infectious, and overall postoperative complications, as well as duration of intensive care unit stay, were significantly reduced in the GEN-EPI group. Stepwise logistic regression demonstrated that the only significant predictors of postoperative cardiovascular complications were preoperative congestive heart failure and general anesthesia without epidural analgesia. We conclude that in patients with atherosclerotic vascular disease undergoing arterial reconstructive surgery (a) thromboelastographic evidence of increased platelet-fibrinogen interaction is associated with early postoperative thrombotic events, and (b) epidural anesthesia and analgesia is associated with beneficial effects on coagulation status and postoperative outcome compared with intermittent on-demand opioid analgesia.