Venoarterial extracorporeal membrane oxygenation (VA-ECMO) often leads to left ventricular (LV) overload, particularly in patients with biventricular cardiogenic shock. This increased afterload can hinder cardiac muscle recovery and cause pulmonary edema, thereby impairing systemic oxygenation. Although devices such as the Impella and intra-aortic balloon pump (IABP) are used to manage this issue, they require complex procedures and pose risks for bleeding and vascular complications. A transseptal approach for left atrial decompression using a single multistage femoral venous cannula provides a simpler solution that avoids the need for additional arterial or venous access. This investigation examined four patients who presented with cardiogenic shock while awaiting transplantation, necessitating mechanical circulatory support using VA-ECMO. This approach includes percutaneous transseptal cannulation of the left atrium (LA), employing the identical multistage venous drainage cannula typically used in VA-ECMO procedures. Guided by real-time transesophageal echocardiography (TEE) and fluoroscopic imaging, a transseptal puncture was performed, followed by advancement of the multistage cannula through the femoral vein into the LA, which ensured effective left atrial decompression, mitigated pulmonary congestion, and reduced LV overload without necessitating additional arterial or venous access. The technique was performed in a hybrid operating room to facilitate precise imaging and procedural control. In a cohort of four patients undergoing VA-ECMO with transseptal cannulation, the venous cannula size was 25 Fr. No major complications such as bleeding, stroke, or tamponade occurred. The mean ECMO flow ranged from 3.5 to 5.0 L/min, with mixed venous oxygen saturation (SVO2) between 65% and 78%. Three patients survived and were discharged after heart transplantation, while one patient died from multiorgan failure unrelated to the procedure. These findings highlight the safety and efficacy of transseptal cannulation for left atrial decompression during VA-ECMO. The transseptal left atrial decompression technique using a single multistage femoral venous cannula offers a simplified, safe, and effective solution for managing LV overload in patients on VA-ECMO. This method eliminates the need for additional access sites and reduces procedural risks, thereby representing a significant advancement in VA-ECMO management. Further large-scale studies are recommended to standardize and evaluate this approach across a broader patient population.