OBJECTIVES: To determine the cost-effectiveness of using a platelet reactivity assay (PRA) to aid in the selection between dual antiplatelet treatment strategies for acute coronary syndrome (ACS) patients. METHODS: A hybrid decision tree/Markov model was used to calculate 5-year costs (2011 US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) of 1-year of universal clopidogrel, ticagrelor or prasugrel (given to all patients) or PRA-driven ticagrelor or prasugrel (given to patients with high platelet reactivity defined as >230 on the VerifyNow P2Y12 assay, others got generic clopidogrel). We assumed a cohort of 65-year-old ACS patients and 32% and 13% incidences of high platelet reactivity ~24-48 hours post-revascularization and at 1-month. The analysis was conducted from a US payer perspective and used a 1-year cycle length. Data depicting the efficacy and safety of dual antiplatelet treatment were taken from randomized trials. RESULTS:  The PRA-driven ticagrelor and prasugrel strategies were cost-effective compared to universal clopidogrel (ICERs=$40,100 and $49,143/QALY); however, universal ticagrelor and prasugrel strategies were not (ICERs=$61,651 and $96,261/QALY).  Monte Carlo simulation suggested PRA-driven ticagrelor, PRA-driven prasugrel, universal ticagrelor and universal prasugrel would have ICERs