Background: There is a clinical need for an intravenous P2Y12 inhibitor in patients with acute coronary syndromes (ACS) for patients who are unable to take oral medications or might benefit from a rapidly reversible compound. As the time from admission to percutaneous coronary intervention (PCI) shortens, establishing the benefit of novel therapies impacting ischemic events is increasingly challenging. Cangrelor, an intravenous potent rapidly acting P2Y12 inhibitor, bolus 30 μg/Kg plus infusion of 4 μg/Kg/min, was compared to a 600-mg loading dose of clopidogrel either before or early after PCI in patients with ACS undergoing PCI in The CHAMPION (Cangrelor versus standard tHerapy to Achieve optimal Management of Platelet InhibitiON) PLATFORM and PCI studies. Methods: As both CHAMPION studies used similar inclusion/exclusion criteria and death, myocardial infarction, or ischemia-driven revascularization (including stent thrombosis) at 48 hours as their primary end points, the studies were pooled. The clinical events committee adjudicated myocardial infarction. The universal definition was used to define myocardial infarction. Results: A total of 13 049 patients were included. Cangrelor had no effect on the primary end point with the original MI definition (P =.646). With the use of the universal definition, the primary end point was decreased with cangrelor (odds ratio 0.82, 95% confidence interval 0.68-0.99, P =.037). Stent thrombosis was reduced from 0.4% to 0.2% (odds ratio 0.44, 95% confidence interval 0.22-0.87, P =.018). Thrombolysis in Myocardial Infarction major bleeding and transfusions were not increased with cangrelor. Conclusion: With the use of the universal definition of myocardial infarction, cangrelor was associated with a significant reduction in early ischemic events when compared with clopidogrel in patients with non-ST-elevation ACS undergoing PCI.