OBJECTIVES: Ticagrelor showed a significant reduction in major cardiac events in patients with acute coronary syndrome (ACS) compared with clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Our aim was to assess the cost-effectiveness of ticagrelor compared to brand and generic clopidogrel in ACS patients from the perspective of the publically funded Canadian health care system. METHODS: A two-part model was developed consisting of a one-year decision tree and a lifetime Markov model. Within the decision tree, patients remained event-free, experienced a non-fatal myocardial infarction (MI), a non-fatal stroke, or death due to vascular or non-vascular related causes based on data from the PLATO trial. The lifetime Markov model followed these patients and allowed subsequent MI, stroke and death. Patient level EQ5D (utility) and resource use were derived from PLATO. Transition probabilities and Canadian unit costs specific were derived from published sources. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: In the base case analysis, one-year of treatment with ticagrelor post-ACS resulted in a lifetime incremental cost-effectiveness ratio (ICER) of $9,745 per quality adjusted life year (QALY) gained, assuming the generic cost for clopidogrel. Compared to brand clopidogrel, the ICER was $1,523 per QALY gained. A probabilistic sensitivity analysis demonstrated a 93% probability of being below $20,000 per QALY gained and a 99% probability of being below $30,000 per QALY gained. CONCLUSIONS: Ticagrelor is a clinically superior and cost-effective option compared to brand and generic clopidogrel for the prevention of major cardiovascular events among ACS patients in Canada.  These results strongly support the reimbursement of ticagrelor for this indication.