Given that patients with prior myocardial infarction and features of high ischemic and low bleeding risk may benefit by extending dual antiplatelet therapy beyond 1 year, we aimed of assessing platelet reactivity provided by ticagrelor 60 mg bid versus prasugrel 5 mg od in 20 such patients participating in a randomized, crossover study. The primary end point of platelet reactivity at the end of the two treatment periods (by VerifyNow, in PRU) was significantly lower for ticagrelor (31.9 PRU [95% CI 12.3–51.4]) compared with prasugrel (132.1 PRU [111.9–152.3]) with a least squares mean difference of –100.2 PRU (72.1–128.3, P < .001). This dedicated pharmacodynamic study showed that in post-myocardial infarction patients with high atherothrombotic risk and receiving P2Y12 receptor antagonist beyond 1 year, low-dose ticagrelor results in a significantly lower platelet reactivity compared to low-dose prasugrel.