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Associations between anesthetic management and cancer recurrence or long-time survival remain uncertain. In this study, we compared the effects of postoperative epidural morphine analgesia with that of postoperative IV fentanyl analgesia on cancer recurrence and long-term survival in patients undergoing resection of hepatocellular carcinoma.A retrospective cohort study was performed on patients with hepatocellular carcinoma receiving hepatic resection at this institution (n = 1846, 1997–2007). Recurrence-free survival and long-term survival were assessed using Kaplan-Meier survival estimates and compared using a multivariate Cox proportional hazards regression, adjusted with propensity scores.Eight hundred nineteen patients met the inclusion criteria and were divided into 2 groups: patients receiving postoperative epidural analgesia with morphine (EA, n = 451) and patients receiving postoperative IV analgesia with fentanyl (IA, n = 368). The median time of follow-up for all patients was 4.2 years (2–9). The rates of recurrence of cancer (37.7% vs 30.7%, P = 0.036) and death (40.6% vs 30.4%, P = 0.003) were higher in the EA group versus IA group. Recurrence-free survival was similar in both the EA and IA groups (hazards ratio 2.224, 95% confidence interval, 0.207–23.893, P = 0.509). Using a multivariate Cox proportional hazards regression adjusted with propensity scores, independent risk factors for long-term survival in patients after resection of hepatocellular carcinoma were ASA physical status, tumor diameter, preoperative α-fetoprotein (+) as well as postoperative epidural analgesia with morphine.Compared with postoperative IV analgesia with fentanyl, postoperative epidural analgesia with morphine was associated with increased cancer recurrence and death but had no significant effect on recurrence-free survival in patients undergoing resection of hepatocellular carcinoma.