Abstract Body (Do not enter title and authors here): Background: Two de-escalation options of dual antiplatelet therapy (DAPT) have been proposed to mitigate bleeding risk in patients (pts) with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI), including maintaining DAPT but reducing its intensity by changing potent P2Y12 inhibitor (P2Y12i) to clopidogrel or discontinuation of DAPT by using P2Y12i monotherapy. Our study aims to evaluate the use of de-escalation therapies after discharge in AMI pts undergoing PCI and compare the clinical outcomes of the two de-escalation options. Methods and Results: In the Taiwan National Health Insurance Research Database, we included adult pts (≥ 18 yrs) who received PCI for AMI and survived to discharge with DAPT. Pts who need oral anticoagulant were excluded. From 2011 to 2021, 58989 pts (mean age 61.9±13.2 yrs, male 81.4%) were included. After 2016, >70% pts were treated with aspirin plus ticagrelor (A+T) at discharge. In A+T users (n=28698), de-escalation for any reason occurred in 52.2% during follow-up. Among de-escalation therapy, aspirin plus clopidogrel (A+C, 55.8%) and ticagrelor monotherapy (T mono, 15.5%) were most commonly used in the first 6 mo. The mean duration from discharge to de-escalation to T mono vs. A+C was 52.5±69.3 vs. 68.4±70.7 days (p<0.01). Multivariable logistic regression analysis showed that multi-vessel PCI and bleeding risk at baseline were more likely to receive T mono than A+C. We used inverse probability of treatment weighting (IPTW) to balance all differences and compared the outcomes after de-escalating to T mono vs. A+C (reference) with Cox proportional hazards analysis. Among pts with multi-vessel PCI, the composite ischemic outcome (cardiovascular death, recurrent MI and ischemic stroke) (HR 0.73, 95% CI 0.50-1.05) and the composite major bleeding outcome (major gastrointestinal bleeding and intracerebral hemorrhage) (HR 0.97, 95% CI 0.46-2.06) were similar between the groups. Among pts with bleeding risk (at least 1 ARC-HBR risk factor), the composite ischemic outcome was similar (HR 1.05, 95% CI 0.76-1.44) and the composite major bleeding outcome was also similar (HR 1.78, 95% CI 0.91-3.50). Conclusions: In pts with AMI undergoing PCI initially received A+T, de-escalation was common after discharge. The clinical outcomes were similar after de-escalating to T mono vs. A+C in pts with multi-vessel PCI or bleeding risk. Further randomized trial is needed to confirm our finding.