Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLTrelated 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations. Conclusion: In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore. (HEPATOLOGY 2015;61:227-237) H epatocellular carcinoma (HCC) is a common cancer with a higher disease burden in East Asia due to the prevalence of chronic viral hepatitis in the region. 8 Emerging data show improving trends in LR outcomes, possibly due to better patient selection, postoperative management, and multimodality treatment for recurrences.9 While recurrence rates in LT are often lower than LR, LT faces considerable resource challenges in many countries, such as the limited supply of cadaveric transplant organs, leading to cancer progression during long waiting times that limit intention-to-treat survival for LT.10 LT patients also require long-term immune suppression, with attendant risks and significant lifetime costs.Randomized trials comparing the two treatments are neither ethical nor practical. Due to the large financial outlay and recurrent costs needed to run a liver transplant program for a large number of HCC patients, 11 the decision to adopt either therapy as a first-line option carries major implications with respect to costs, utility of scarce re...