OBJECTIVES The aim of this study was to evaluate the long-term cost effectiveness of ticagrelor + aspirin versus clopidogrel + aspirin in patients with acute coronary syndrome (ACS) treated for 12 months in Spain. METHODS The cost effectiveness model consisted of a decision tree (1st year) based on the PLATO study and a long-term Markov model (2nd year onwards). This allowed estimation of cardiovascular events (death, myocardial infarction and non-fatal stroke), survival, health costs, and health related quality of life. A life time horizon was applied. The daily drug cost was € 0.60 and €2.96 for generic clopidogrel and ticagrelor, respectively. Spanish unit costs and life tables were used; outcomes and costs were discounted at 3%.  A sensitivity analysis across subgroups was carried out, and probabilistic sensitivity analysis was used to validate the robustness of the model. RESULTS Ticagrelor compared to clopidogrel was associated with a gain of 0.1586 life years and 0.1363 years of quality-adjusted life years (QALY), with an incremental cost of € 596. The incremental cost per life year and per QALY gained was € 3,760 and € 4,374, respectively. The probabilistic sensitivity analysis showed that ticagrelor was cost-effective versus clopidogrel in >99 % of the simulations given a willingness-to-pay threshold of € 15,000/QALY. The results were consistent across different subgroups of ACS patients. CONCLUSIONS Ticagrelor + aspirin for 12 months is a cost effective treatment compared to generic clopidogrel + aspirin in patients with ACS treated invasively or conservatively, based on the findings of the PLATO study and Spanish health care costs.