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Background: Percutaneous ventricular assist devices and extracorporeal membrane oxygenation (ECMO) are increasingly used for mechanical circulatory support (MCS) in patients with acute myocardial infarction with cardiogenic shock (AMI-CS) in hospitals throughout the United States., Methods: Using the National Inpatient Sample from October 2015 to December 2017, we identified hospital admissions that underwent percutaneous coronary intervention (PCI) and non-elective Impella or ECMO placement for AMI-CS using ICD-10 codes. Propensity-score matching was performed to compare both groups for primary and secondary outcomes., Results: We identified 6290 admissions for AMI-CS who underwent PCI and were treated with Impella (n = 5730, 91%) or ECMO (n = 560, 9%) from October 2015 to December 2017. After propensity-match analysis, the ECMO cohort had significantly higher in-hospital mortality (43.3% vs 26.7%, OR: 2.10, p = 0.021). The incidence of acute respiratory failure and vascular complications were significantly lower in the Impella cohort. We observed a shorter duration of hospital stay and lower hospital costs in the Impella cohort compared to those who received ECMO., Conclusions: In AMI-CS, the use of Impella was associated with better clinical outcomes, fewer complications, shorter length of hospital stay and lower hospital cost compared to those undergoing ECMO placement., Competing Interests: Declaration of competing interest Dr Basir has the following disclosures: Abbott Vascular, Abiomed, Chiesi, Cardiovascular Systems, and Zoll. Dr Kapur has the following disclosures: Abbott, Abiomed, Boston Scientific, Medtronic, LivaNova, MD Start, and Precardia. Dr O'Neill has the following disclosures: Abiomed and Abbott. The rest of the authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)