OBJECTIVES: To critically appraise published pharmacoeconomic studies of two novel antiplatelet (AP) agents (ticagrelor and prasugrel) in the treatment of acute coronary syndromes (ACS). METHODS: Key terms related to economic evaluations of ticagrelor and/or prasugrel were searched in EMBASE, MEDLINE and International Pharmaceutical Abstracts. English-language articles evaluating the use of these agents in adults with ACS were included. Studies assessing genotyping-guided treatments were excluded. Elements of each study were independently extracted based on the ISPOR Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist by two reviewers. RESULTS: Eleven (7 ticagrelor, 4 prasugrel) studies were identified, 7 of which included both cost-effectiveness and cost-utility analysis. No comparisons were made between prasugrel and ticagrelor and each agent was compared to clopidogrel. The manufacturer of the novel AP funded all but one study. Most models were Markov-based simulations, with almost all studies adopting a healthcare system perspective and lifetime time horizon. Two randomized-control trials (RCTs), PLATO and TRITON-TIMI 38 were most commonly cited for ticagrelor and prasugrel, respectively, with few non-RCTs used for clinical data input. While methods to derive the efficacy data were commonly reported, utility estimates varied for some health states between studies using the same data by the same sponsor. Both ticagrelor and prasugrel were deemed cost-effective vs. clopidogrel in base-case analyses. CONCLUSIONS: Studies would benefit from greater consistency in sources of costing data and estimates of utility values and decrements. There is a clear reliance on single multinational RCTs as the primary data source for the vast majority of model inputs, and the PLATO study has been heavily criticized for issues related to external validity. More independent, non-industry sponsored economic evaluations and real-world clinical data are required in the future. Reporting checklists do not capture these latent issues behind economic evaluations, as identified by our appraisal of the literature.