The aim of this study was to confirm whether intravenous anaesthesia supplemented with the N-methyl-d-aspartate (NMDA) antagonist ketamine could reduce post-operative pain after elective open cholecystectomy. Fifty patients were randomised double-blind to one of the following two groups: PF Group received propofol and fentanyl supplemented with saline infusion; PFK Group received propofol and fentanyl supplemented with ketamine (total dose 2mg/kg). During the first 48 post-operative hours, epidural analgesia was provided for all patients with patient-controlled epidural analgesia (PCEA) using 0.125% bupivacaine and morphine (0.05mg/ml). Pain assessments at rest and movement, and cumulative PCEA volume consumed, were recorded at 5, 24 and 48h post-operatively. The visual analogue scale (VAS) scores at rest were significantly less in the PFK Group than in the PF Group at 5, 24 and 48h (P<0.001, P<0.001 and P=0.02, respectively). The VAS score at movement were also significantly (P<0.001) less throughout this study than in the PF Group. The difference in PCEA analgesic consumption at 0-5 and 5-24h reached statistical significance (P<0.001 and P=0.008, respectively). Our results show that an intra-operative ketamine dose provides advantages for post-operative analgesia beyond its duration of action after an open cholecystectomy.