Abstract Objective While Opioid Use Disorder (OUD) has been linked to inferior clinical outcomes, studies examining the clinical outcomes and readmission of OUD patients experiencing Acute Myocardial Infarction (AMI) remain lacking. The authors analyze the clinical and financial outcomes of OUD in a contemporary cohort of AMI hospitalizations. Methods All non-elective adult (≥ 18 years) hospitalizations for AMI were tabulated from the 2016‒2019 Nationwide Readmissions Database using relevant International Classification of Disease codes. Patients were grouped into OUD and non-OUD cohorts. Bivariate and regression analyses were performed to identify the independent association of OUD with outcomes after non-elective admission for AMI, as well as subsequent readmission. Results Of an estimated 3,318,257 hospitalizations for AMI meeting study criteria, 36,057 (1.1%) had a concomitant diagnosis of OUD. While OUD was not significantly associated with mortality, OUD patients experienced superior cardiovascular outcomes compared to non-OUD. However, OUD was linked to increased odds of non-cardiovascular complications, length of stay, costs, non-home discharge, and 30-day non-elective readmission. Conclusions Patients with OUD presented with AMI at a significantly younger age than non-OUD. While OUD appears to have a cardioprotective effect, it is associated with several markers of increased resource use, including readmission. The present findings underscore the need for a multifaceted approach to increasing social services and treatment for OUD at index hospitalization. (OUD (AMI lacking nonelective non elective ≥ ( 1 years 20162019 2016 2019 2016‒201 codes nonOUD cohorts 3318257 3 318 257 3,318,25 criteria 36057 36 057 36,05 1.1% 11 (1.1% mortality nonOUD. However noncardiovascular complications stay costs nonhome home discharge 30day day 30 effect use hospitalization 2016201 201 2016‒20 331825 31 25 3,318,2 3605 05 36,0 1.1 (1.1 201620 20 2016‒2 33182 2 3,318, 360 0 36, 1. (1. 20162 2016‒ 3318 3,318 (1 331 3,31 33 3,3 3,