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Postoperative analgesia and care for living liver donors have become particular interests for clinicians as the use of living donor liver transplantation has increased. Local anesthetic–based analgesia has been known to provide effective pain control. In this prospective, randomized study, we compared the postoperative analgesic efficacy of local anesthetic–based analgesia (PainBuster) with the efficacy of opioid-based analgesia [intrathecal morphine (ITM) with intravenous (IV) fentanyl] in liver donors. Forty adult donors were randomly allocated to 1 of 2 groups: an ITM/IV fentanyl group (n = 21) and a PainBuster group (n = 19). Donors in the PainBuster group received 0.5% ropivacaine via a multi-orifice catheter (ON-Q PainBuster) placed at the wound. Donors in the ITM/IV fentanyl group received ITM sulfate (400 μg) preoperatively and a continuous IV fentanyl infusion postoperatively. A visual analogue scale (VAS) at rest and with coughing and rescue IV fentanyl and meperidine consumption were assessed for 72 hours after the operation. Side effects, including sedation, dizziness, nausea, vomiting, pruritus, respiratory depression, wound seroma or hematoma, and the first time to flatus, were recorded. The VAS score at rest during the first 12 postoperative hours was significantly lower for the ITM/IV fentanyl group. At other times, the VAS scores were comparable between the groups. In the PainBuster group, rescue IV fentanyl and meperidine use was significantly reduced 24 to 48 hours and 48 to 72 hours after surgery in comparison with the first 24 postoperative hours. The time to first flatus was significantly reduced in the PainBuster group. There were no differences in side effects. In conclusion, analgesia was more satisfactory with ITM/IV fentanyl versus PainBuster during the first 12 hours after surgery, but they became comparable thereafter, with a shortened bowel recovery time in the PainBuster group. The concurrent use of ITM with PainBuster may be considered in a future investigation. Liver Transpl 19:1036–1045, 2013. © 2013 AASLD.