A prospective, randomized study was used to compare 2 anesthesia/analgesia methods for reconstructive spine surgery. To assess the efficacy and influence of 2 anesthetic methods on clinical outcome and stress response during reconstructive spine surgery. Pain control is an important goal of the postoperative care after spinal surgery. Some prior studies have suggested that epidural anesthesia with or without postoperative epidural analgesia may blunt the surgical stress response after major surgery. This treatment approach has not been fully investigated for patients undergoing major spinal surgery. We hypothesized that the stress response after major spine surgery would be attenuated by continuous epidural anesthesia/analgesia with ropivacaine, fentanyl, and epinephrine. Eighty-five patients were randomly allocated to 2 groups as follows: group E (n = 45) had epidural anesthesia and endotracheal anesthesia with sevoflurane during surgery and continuous epidural analgesia with ropivacaine, fentanyl, and epinephrine after surgery; group G (n = 40) had general anesthesia with sevoflurane and fentanyl and systemically administered opioids after surgery. Patient pain, nausea, mobility, and satisfaction were measured after surgery along with levels of cortisol, glucose, interleukin (IL)-1β, IL-6, and IL-10 during and after surgery. In group E, there were significantly less pain, less nausea, earlier mobility, and higher satisfaction than those in group G. Group E also experienced significantly less introperative and postoperative blood loss. Group E demonstrated lower levels of glucose, cortisol, IL-1β, IL-6, and IL-10 during the postoperative period. Combined epidural/general anesthesia and postoperative epidural analgesia produced better pain control, less bleeding, and a lower surgical stress response than general anesthesia with postoperative systemically administered narcotic analgesia. This technique deserves further study in the setting of major spinal surgery.