The impact of extracorporeal membrane oxygenation (ECMO) support on coronary blood flow and left ventricular unloading is still debated. This study aimed to further characterize the influence of ECMO on coronary artery blood flow and its ability to unload the left ventricle in a short-term model of acute cardiogenic shock. Seven anesthetized pigs were intubated and then underwent median sternotomy and cannulation for venoarterial (VA) ECMO. Flow in the left anterior descending (LAD) artery, left atrial pressure (LAP), left ventricular end-diastolic pressure (LVEDP), and mean arterial pressure (MAP) were measured before and after esmolol-induced cardiac dysfunction and after initiating VA-ECMO support. Induction of acute cardiogenic shock was associated with short-term increases in LAP from 8 ± 4 mm Hg to 18 ± 14 mm Hg (P = 0.9) and LVEDP from 5 ± 2 mm Hg to 13 ± 17 mm Hg (P = 0.9), and a decrease in MAP from 63 ± 16 mm Hg to 50 ± 24 mm Hg (P = 0.3). With VA-ECMO support, blood flow in the LAD increased from 28 ± 25 mL/min during acute unsupported cardiogenic shock to 67 ± 50 mL/min (P = 0.003), and LAP and LVEDP decreased to 8 + 5 mm Hg (P = 0.7) and 5 ± 3 mm Hg (P = 0.5), respectively. In this swine model of acute cardiogenic shock, VA-ECMO improved coronary blood flow and provided some degree of left ventricular unloading for the short duration of the study.