Background: Purinergic signaling receptor Y12(P2Y12) inhibitors are a fundamental part of pharmacological therapy in acute coronary syndrome (ACS) for preventing recurrent ischemic events. Current guidelines support the use of prasugrel over ticagrelor—however, ticagrelor is widely used for preclinical loading during ACS due to its ease of administration. In this regard, it remains unknown whether the preclinical loading with P2Y12inhibitors impacts decision-making for the long-term dual antiplatelet strategy, as well as cardiovascular outcomes, including re-percutaneous coronary intervention in real-world settings. Methods: Within this population-based prospective observational study, all patients with ACS who received medical care via the Emergency Medical Service (EMS) in the city of Vienna between January 2018 and October 2020 were enrolled. Patients were stratified according to their P2Y12inhibitor loading regimen. Subsequently, the association of P2Y12inhibitor loading on long-term prescription at discharge and outcome was assessed. Results: The entire study cohort consisted of 1176 individuals with ST-elevation myocardial infarction (STEMI), of whom 47.5% received prasugrel and 52.5% ticagrelor. The likelihood of adhering to the initial P2Y12inhibitor strategy during the clinical stay was high for both ticagrelor (84%; OR: 10.00;p< 0.001) and prasugrel (77%; OR: 21.26;p< 0.001). During patient follow-up (median follow-up time three years), 84 (7.1%) patients died due to cardiovascular causes, and 82 (7.0%) patients required re-PCI. Notably, there was no difference in cardiovascular mortality (6.6% ticagrelor vs. 7.7% prasugrel) or re-PCI rates (6.6% ticagrelor vs. 7.3% prasugrel) addressing the P2Y12inhibition strategy. Conclusion: We observed that, regardless of the initial antiplatelet inhibitor strategy, the in-hospital P2Y12adherence was exceedingly high, and there was a minimal occurrence of switching to another P2Y12inhibitor. Most importantly, no significant difference in cardiovascular death/re-PCI between ticagrelor and prasugrel-based preclinical loading has been observed. Consequently, the choice of high potent P2Y12did not influence the cardiac outcome from a long-term perspective.