Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with profound left ventricular (LV) failure is associated with inadequate LV emptying. To unload the LV, VA-ECMO can be combined with Impella CP (ECMELLA). We hypothesized that ECMELLA improves cardiac energetics compared with VA-ECMO in a porcine model of cardiogenic shock (CS). Land-race pigs (weight 70kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. CS was induced with embolization in the left main coronary artery. CS was defined as reduction of ≥50% in cardiac output or mixed oxygen saturation (SvO2) or a SvO2<30%. At CS VA-ECMO was initiated and embolization was continued until arterial pulse pressure was <10mmHg. At this point, Impella CP was placed in the ECMELLA arm. Support was maintained for 4h. CS was induced in 15 pigs (VA-ECMO n=7, ECMELLA n=8). At time of CS MAP was <45mmHg in both groups, with no difference at 4h (VA-ECMO 64mmHg±11 vs. ECMELLA 55mmHg±21, P=0.08). Carotid blood flow and arterial lactate increased from CS and was similar in VA-ECMO and ECMELLA [239mL/min±97 vs. 213mL/min±133 (P=0.6) and 5.2±3.3 vs. 4.2±2.9mmol/ (P=0.5)]. Pressure-volume area (PVA) was significantly higher with VA-ECMO compared with ECMELLA (9567±1733 vs. 6921±5036mmHg×mL/min×10-3, P=0.014). Total diureses was found to be lower in VA-ECMO compared with ECMELLA [248mL (179-930) vs. 506mL (418-2190); P=0.005]. In a porcine model of CS, we found lower PVA, with the ECMELLA configuration compared with VA-ECMO, indicating better cardiac energetics without compromising systemic perfusion.