A prasugrel-based strategy is associated with a lower incidence of death, myocardial infarction (MI) or stroke than a ticagrelor-based strategy in patients with an acute coronary syndrome (ACS) with or without ST-segment elevation who are scheduled to undergo invasive evaluation. These findings come from the ISAR-REACT 5 trial, conducted in Germany and Italy, and were presented at the ESC Congress 2019. Patients assigned to ticagrelor (n = 2,012) received the loading dose as soon as possible after randomization; in the prasugrel group (n = 2,006), therapy was initiated as soon as possible after randomization in patients with ST-segment elevation but was postponed until after assessment of the coronary anatomy for those without ST-segment elevation. The rate of the primary end point (a composite of death, MI or stroke at 1 year) was 9.3% with ticagrelor and 6.9% with prasugrel (HR 1.36, 95% CI 1.09–1.70, P = 0.006). The lower incidence of the primary end point with prasugrel was driven by fewer MIs. The rate of major bleeding events was not significantly different between the groups.