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Background: The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI)., Objectives: The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI., Methods: A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization., Results: As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients)., Conclusions: COVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations., Competing Interests: Funding Support and Author Disclosures This work was supported by an American College of Cardiology Accreditation Grant, Saskatchewan Health Research Foundation (SHRF), and grants from Medtronic and Abbott Vascular to SCAI. Dr. Garcia has received institutional research grants from Edwards Lifesciences, BSCI, Medtronic, and Abbott Vascular; has served as a consultant for Medtronic and BSCI; and has served as a proctor for Edwards Lifesciences. Dr. Saw has received unrestricted research grant support from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, National Institutes of Health, AstraZeneca, Abbott Vascular, St. Jude Medical, Boston Scientific, and Servier; has received salary support from the Michael Smith Foundation for Health Research; has received speaker honoraria from AstraZeneca, Abbott Vascular, Boston Scientific, and Bayer; has received consultancy and advisory board honoraria from AstraZeneca, Boston Scientific, Abbott Vascular, Gore, Abiomed, and Baylis; and has received proctorship honoraria from Abbott Vascular and Boston Scientific. Dr. Jaffer has received research grants from Siemens, Canon, Shockwave, and Teleflex; has served as a consultant for Boston Scientific, Siemens, Biotronik, and Magenta Medical; owns equity interest in Intravascular Imaging; and Massachusetts General Hospital has patent licensing arrangements with Canon, Terumo, and Spectrawave, and Dr. Jaffer has a right to receive licensing royalties. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. All rights reserved.)