Abstract Funding Acknowledgements None. Background/Introduction Antiplatelet therapy is the cornerstone treatment for ST-segment elevation myocardial infarction (STEMI). Dual antiplatelet therapy (DAPT) including aspirin and a potent P2Y12 inhibitor (P2Y12i) is recommended as the default strategy. However, the timing of DAPT remains controversial: European Cardiology Society (ESC) guidelines ceased recommending pretreatment with P2Y12i in STEMI, based on ATLANTIC trial results. Purpose This study aims to evaluate the effect of DAPT with potent P2Y12i pretreatment DAPT in STEMI patients, comparing with DAPT with clopidogrel and aspirin only pretreatment. Methods We have analyzed the antiplatelet pretreatment strategy results of a retrospective cohort of 2283 STEMI patients, from a multicenter national registry, from 2011 till 2019. We compared 3 groups: DAPT with potent P2Y12i, DAPT with clopidogrel and aspirin only. Primary endpoints were death, major adverse cardiovascular events (MACE), including reinfarction, heart failure, sustained ventricular arrhythmia, cardiogenic shock, mechanical complication and stroke, and successful PCI. Safety endpoint was major hemorrhagic events between different strategies. Results A total of 2283 STEMI patients where included, with a mean age of 66±13 years and 27% (n=627) were female. The population was divided in 3 groups, according with pretreatment strategy: DAPT with potent P2Y12i, DAPT with clopidogrel and aspirin only. 334 patients undergone DAPT with potent P2Y12i, and 86% (n=296) had a successful PCI, 21% (n=69) had a MACE and 9% (n=31) died in hospital. The group of patients submitted to DAPT with clopidogrel were 1815, and 80% (n=1448) had a successful PCI, 29% (n=527) had a MACE and 11,5% (n=209). The group pretreated only with aspirin were 124 patients, of which, only 14% (n=17) had a successful PCI, 38% (n=47) had a MACE and 39% (n=49) died. Regarding safety outcomes, 1,5% (n=5) patients with DAPT with potent P2Y12i had a significant hemorrhage, comparing with 3% (n=53) of patients with DAPT with clopidogrel and 3% (n=4) of aspirin only group of patients. There was a statistically significant higher rate of successful PCI with DAPT with potent P2Y12i (p<0,05 OR 2), a statistically significant lower number of MACE (p<0,05 OR 0,6) and in hospital deaths (p=0,04 OR 0,67), comparing with DAPT with clopidogrel and aspirin only groups. There was no statistically significant difference between groups in terms of hemorrhagic events (p=0,7). According to our retrospective multicenter national registry, pretreatment with potent P2Y12i is associated with better results, namely higher rate of successful PCI, less MACE and in hospital death, contrary to recent trials. Our study has some bias: the pretreatment with DAPT was standard of care during the registry, and the choice for aspirin only strategy might be due to higher risk patients, as the choice was not randomized.Antiplatelet treatment comparison