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Animal studies suggest that regional anesthesia and optimal postoperative analgesia independently reduce cancer metastasis. Retrospective clinical studies suggest reductions in recurrence of several cancer types in patients receiving perioperative neuraxial analgesia. Thus, the authors determined the association between perioperative epidural analgesia and cancer recurrence in patients undergoing colorectal cancer surgery.After obtaining approval of institutional review board, the authors reviewed the records of 669 patients undergoing colorectal cancer surgery between January 2000 and March 2007. Follow-up ended in November 2008. The authors' primary outcome was time to cancer recurrence. Cox proportional hazards models were used.Two hundred fifty-six patients who received epidural analgesia and 253 who did not were analyzed in a multivariable model to assess the association between epidural use and cancer recurrence. Overall, no association between epidural use and recurrence was found (P = 0.43), with an adjusted estimated hazard ratio of 0.82 (95% CI 0.49–1.35). In post hoc analyses, epidural use was associated with a lower cancer recurrence in older patients (age older than 64 yr), but not in younger (interaction P = 0.01). A sensitivity analysis using propensity score analysis found similar results.In contrast to previous retrospective studies in the colon, breast, and prostate cancer surgery, the authors found that the use of epidural analgesia for perioperative pain control during colorectal cancer surgery was not associated with a decreased cancer recurrence; however, a potential benefit was observed in older patients. The benefit of regional anesthesia on cancer recurrence may thus depend on the specific tumor type.