The peripheral venoarterial extracorporeal life support (V-A ECLS) in cardiogenic shock (CS) may lead to LV overload. The transaortic suction device (Impella, ABIOMED Inc., Danvers, MA) was compared to the pulmonary artery (PA) drainage, for LV unloading efficacy during V-A ECLS in a porcine cardiogenic shock model. A dedicated CS model included 12 swine (21 ± 1.8-week-old and weighing 54.3 ± 4.6 kg) supported with V-A ECLS and randomized to Impella or PA-related LV drainage. LV unloading and end-organ perfusion were evaluated through the PA catheter and LV pressure/volume analysis. The LV end-diastolic volume sharply dropped with Impella (143.6 ± 67.4 vs 123 ± 75.7 mL) compared to a slight decrease in the PA cannula group (134.1 ± 39.9 vs 130.1 ± 34.7 mL), resulting in an overall stroke work and pressure-volume area reductions with both techniques. However, stroke work reduction was more significant in the Impella group (V-A ECLS 3998.8 ± 2027.6 vs V-A ECLS + Impella 1796.9 ± 1033.9 mm Hg × mL, P = 0.016), leading to a more consistent pressure-volume area reduction (Impella reduction 34.7% vs PA cannula reduction 9.7%) In terms of end organ perfusion, central and mixed O2 saturation improved with V-A ECLS, and subsequently, remaining unchanged with either Impella or PA cannula as unloading strategy (SVmO2: Impella 86.0 ± 5.8 vs 87.8 ± 5.8; PA cannula 82.5 ± 10.7 vs 82.5 ± 11.3 %). Transaortic suction and PA drainage provided effective LV unloading during V-A ECLS while maintaining adequate end-organ perfusion. Impella provides a greater LV unloading effect and reduces more effectively the total LV stroke work.