OBJECTIVES: PLATO was a multi centered, double blind, randomized study that included 18,624 ACS patients from 43 countries, comparing ticagrelor + aspirin versus clopidogrel + aspirin. The PLATO demonstrated that ticagrelor was superior on the primary composite endpoint: myocardial infarction, stroke, cardiovascular death (HR 0.84, 95% CI: 0.77 to 0.92) without an increase in major bleedings compared to clopidogrel, and whether the strategy of choice was invasive or conservative. The aim of this analysis is to estimate direct health care costs from a Spanish health care perspective (excluding drug costs because ticagrelor price has not yet been established). METHODS: Resource utilization was pre specified in the PLATO trial and included hospitalization bed days, investigations, interventions and blood products. Direct health care costs per patient at 12 months were estimated by multiplying the resource use with Spanish unit costs derived from the Spanish database e-salud, the GRDs of the Ministry of Health, published literature, and the CMBD 2008.  RESULTS: Ticagrelor resulted in numerically fewer bed days (mean difference per patient 0.21, 95% CI -0.16 to 0.59), PCIs (mean difference per patient 0.01, 95% CI -0.01 to 0.03) and CABGs (mean difference per patient 0.01, 95% CI: 0.00 to 0.01). Ticagrelor is associated with €341 reduction per patient (95% CI: 31 to 652) in healthcare costs at 12 months compared to clopidogrel. The reduction in healthcare costs was mainly due to fewer hospital days and cardiovascular interventions in the ticagrelor group. The reduction in cost increased over the 12-month treatment period consistent with the rate of clinical events over time in the PLATO study.  CONCLUSIONS: Treatment with ticagrelor is associated with cost savings in patients with ACS at 12 months compared with clopidogrel (excluding drug costs) from a Spanish health care perspective. However, the total cost savings will depend on drug price, data not available yet.