Objective: To describe a case of cardiac arrest (CA) associated with protamine induced vasoplegic syndrome (PIVS), managed with the Cardiac Advanced Life Support (CAL S) protocol and extracorporeal life support (ECLS) using extracorporeal membrane oxygenation (ECMO). Case report: A 51-year-old male patient with multiple valvular diseases underwent mitral valve replacement and tricuspid annuloplasty. In the immediate postoperative period, while still in the operating room, he developed severe protamine-induced hypotension, followed by asystolic CA. He was managed with direct cardiac massage, reconnection to extracorporeal circulation (ECC), and vasopressor infusion, achieving return of spontaneous circulation (ROSC) after 15 minutes. Following the patient's hemodynamic stabilization, sternotomy closure and ECC discontinuation were performed. In the Coronary Intensive Care Unit, he experienced another asystolic CA, unresponsive to advanced resuscitation maneuvers. A re-sternotomy and ECLS with femoral vein-arterial ECMO (FV-FA) were performed, achieving ROSC. During the intervention, a left ventricular wall rupture secondary to direct massage was identified and successfully repaired. The patient remained on ECMO for 12 days and evolved without neurological sequelae. Discussion: PIVS was the triggering factor, worsened by multifactorial refractory shock. The implementation of ECLS with ECMO and a trained multidisciplinary team was crucial for the patient's survival. Conclusions: ECLS with ECMO, used within 30 minutes, in conjunction with the CALS protocol, improves survival and prevents neurological sequelae in cases with protamine-induced vasoplegic syndrome.