Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties in addition to inhibiting serine proteases. Administration of human plasma–derived AAT is protective in models of acute myocardial infarction in mice. The objective of this study was to determine the safety and tolerability of human plasma–derived AAT and its effects on the acute inflammatory response in non-AAT deficient patients with ST-segment elevation myocardial infarction (STEMI). Ten patients with acute STEMI were enrolled in an open-label, single-arm treatment study of AAT at 60 mg/kg infused intravenously within 12 hours of admission and following standard of care treatment.