Ventricular septal rupture (VSR) is a rare but often fatal complication of acute myocardial infarction (AMI), with a high mortality largely driven by resultant cardiogenic shock. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides emergency circulatory support and may improve outcomes. We retrospectively analyzed the Extracorporeal Life Support Organization (ELSO) Registry to identify adults (≥18 years) with post-AMI VSR receiving preoperative VA-ECMO (2000–2025). Clinical characteristics were compared between survivors and nonsurvivors. The primary outcome was in-hospital survival. Among 370 patients, the median age was 66 years, 70% were male, and 66% were in cardiogenic shock at ECMO initiation. Inferior AMI occurred in 56%, and 56% had prior mechanical circulatory support. In-hospital mortality was 68%. Survivors were significantly younger (median 62 vs. 67 years) and had lower rates of pre-ECMO cardiac arrest (7% vs. 21%), tamponade (2% vs. 8%), and renal replacement therapy (21% vs. 37%). Survivors also experienced longer duration of ECMO support and hospital length of stay. While rescuing many patients in post-AMI VSR-related shock, mortality remains high. Identifying predictors of survival and optimizing perioperative management are essential to improve outcomes in this high-risk group.