Abstract Body (Do not enter title and authors here): Background: ST-segment-elevation myocardial infarction (STEMI) is estimated to affect approximately 250,000 people in the US each year, leading to significant burden of morbidity and mortality. Evidence on long-term outcomes following percutaneous coronary intervention (PCI) for STEMI is limited. Aims: To assess clinical and economic outcomes following PCI among patients with STEMI. Methods: This retrospective study utilizing data from Premier PINC AI™ Healthcare Database was conducted among adult patients (age ≥ 18 years) discharged from US hospitals for PCI with a primary diagnosis of STEMI, between October 1, 2016 and December 31, 2021 (index date). The study included mortality data from an external data source that captures death dates for approximately 85% of the US population. Clinical outcomes, healthcare resource use, and costs (adjusted to 2022 US dollars) following first PCI discharge were assessed for a minimum of 1 year. Outcomes at 3-year follow up were assessed among a subset of patients with an index date on or before December 31, 2019. Multivariable regression was used to identify risk factors for key outcomes. Results: A total of 180,691 patients underwent PCI for STEMI in 633 US hospitals during the study period. Median age of patients was 62 years, with majority being male (71%), White (79.1%), and with Medicare as the primary payor (42.9%). At index visit, 13.8% of patients had ventricular tachycardia, 8.8% had ventricular fibrillation, with a median cost of $17,582, and a mortality rate of 5.5%. Within 1-year, there were 1,966 (1.1%) additional deaths, 16.4% of patients were readmitted, 12.6% newly diagnosed with heart failure (HF), 3.6% with atrial fibrillation, and 1% experienced recurrent STEMI. The median total study cost at 1-year was $21,010. In patients with 3-year follow up data (n=63,469), the mortality rate was 7.5%. Charlson Comorbidity Index (CCI) score ≥4 (vs <4) at index visit was most strongly associated with higher risk of death at follow up periods: 1-year (HR: 4.1, 95% CI: 3.66 to 4.49), 3-year (HR: 3.7, 95% CI: 3.21 to 4.27), higher odds of readmissions (1,3-year: OR: 2.2, 95% CI: 2.08 to 2.37), HF incidence (OR: 3.0 to 3.2, 95% CI: 2.89 to 3.35) and had 74% higher costs (p<0.05). Conclusion: This study highlights the risk factors associated with long-term negative clinical outcomes and higher cost following PCI for the treatment of STEMI.