This study examines the challenges of estimating risk-adjusted treatment costs in international comparative research, specifically in the European Health Care Outcomes, Performance, and Efficiency (EuroHOPE) project. We describe the diverse format of resource data and challenges of converting these data into resource use indicators that allow meaningful cross-country comparisons. The three cost indicators developed in EuroHOPE are then described, discussed, and applied. We compare the risk-adjusted mean treatment costs of acute myocardial infarction for four of the seven countries in the EuroHOPE project, namely, Finland, Hungary, Norway, and Sweden. The outcome of the comparison depends on the time perspective as well as on the particular resource use indicator. We argue that these complementary indicators add to our understanding of the variation in resource use across countries. Copyright © 2015 John Wiley & Sons, Ltd.