BACKGROUND—Postinfarction ventricular septal defect carries a grim prognosis. Surgical repair offers reasonable outcomes in patients who survive a healing phase. Percutaneous device implantation represents a potentially attractive early alternative. METHODS AND RESULTS—Postinfarction ventricular septal defect closure was attempted in 53 patients from 11 centers (1997–2012; aged 72±11 years; 42% female). Nineteen percent had previous surgical closure. Myocardial infarction was anterior (66%) or inferior (34%). Time from myocardial infarction to closure procedure was 13 (first and third quartiles, 5–54) days. Devices were successfully implanted in 89% of patients. Major immediate complications included procedural death (3.8%) and emergency cardiac surgery (7.5%). Immediate shunt reduction was graded as complete (23%), partial (62%), or none (15%). Median length of stay after the procedure was 5.0 (2.0–9.0) days. Fifty-eight percent survived to discharge and were followed up for 395 (63–1522) days, during which time 4 additional patients died (7.5%). Factors associated with death after postinfarction ventricular septal defect closure included the followingage (hazard ratio HR=1.04; P=0.039), female sex (HR=2.33; P=0.043), New York Heart Association class IV (HR=4.42; P=0.002), cardiogenic shock (HR=3.75; P=0.003), creatinine (HR=1.007; P=0.003), defect size (HR=1.09; P=0.026), inotropes (HR=4.18; P=0.005), and absence of revascularization therapy for presenting myocardial infarction (HR=3.28; P=0.009). Prior surgical closure (HR=0.12; P=0.040) and immediate shunt reduction (HR=0.49; P=0.037) were associated with survival. CONCLUSIONS—Percutaneous closure of postinfarction ventricular septal defect is a reasonably effective treatment for these extremely high-risk patients. Mortality remains high, but patients who survive to discharge do well in the longer term.