Several tumor response criteria on cross-sectional imaging have been used in hepatocellular cancer after locoregional, intra-arterial therapy. The cost implications of their efficacy and accuracy are not well established. To evaluate cost-effectiveness of quantitative European Association for Study of the Liver (qEASL) compared with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) response criteria. A Markov decision-analytic model was constructed, accounting for both costs and outcomes from a payor perspective. Three different tumor imaging response criteria were evaluated: (1) qEASL, (2) RECIST, and (3) mRECIST. Input parameters were derived from the most comprehensive literature available focusing on the assessment of liver tumor response after transarterial chemoembolization. Deterministic and probabilistic sensitivity analyses were performed. Base case calculation showed qEASL to be the dominant strategy, with the highest effectiveness (1.06 quality-adjusted life years (QALY), as compared with 1.05 QALY in mRECIST and 1.02 QALY in RECIST). The expected costs of qEASL, mRECIST, and RECIST were $451,773, $460,489, and $459,004, respectively. qEASL was more cost-effective than RECIST in 71.50% of the 10,000 iterations and mRECIST in 69.26% of the iterations. One-way sensitivity analysis varying the cost showed that qEASL remained cost-effective until its additional cost was above $9,994. Our study demonstrates qEASL to be the most cost-effective tumor response assessment criterion, with substantial cost savings as compared with RECIST and mRECIST for patients with hepatocellular carcinoma after transarterial chemoembolization. Copyright © 2020 American College of Radiology. Published by Elsevier Inc. All rights reserved.