Background Off‐target properties of ticagrelor might reduce microvascular injury and improve clinical outcome in patients with ST‐segment–elevation myocardial infarction. The REDUCE‐MVI (Evaluation of Microvascular Injury in Revascularized Patients with ST‐Segment–Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel) trial reported no benefit of ticagrelor regarding microvascular function at 1 month. We now present the follow‐up data up to 1.5 years. Methods and Results We randomized 110 patients with ST‐segment–elevation myocardial infarction to either ticagrelor 90 mg twice daily or prasugrel 10 mg once a day. Platelet inhibition and peripheral endothelial function measurements including calculation of the reactive hyperemia index and clinical follow‐up were obtained up to 1.5 years. Major adverse clinical events and bleedings were scored. An intention to treat and a per‐protocol analysis were performed. There were no between‐group differences in platelet inhibition and endothelial function. At 1 year the reactive hyperemia index in the ticagrelor group was 0.66±0.26 versus 0.61±0.28 in the prasugrel group (P=0.31). Platelet inhibition was lower at 1 month versus 1 year in the total study population (61% [42%–81%] versus 83% [61%–95%]; P