BACKGROUND Ventricular septal defect (VSD) after acute myocardial infarction is a catastrophic event. OBJECTIVE We describe our multicentre experience of a defect closure strategy that combined surgery and transcatheter closure. METHODS Data were obtained by retrospective chart review. RESULTS Twenty patients (mean age, 67 years) from three centres were studied. Median time from myocardial infarction to VSD was 6 (range, 3-9) days. Acute cardiogenic shock occurred in 12 (60%) patients. Median defect diameter by echocardiography was 18 (range, 12-28) mm. Median time to first surgical or percutaneous closure was 18 (range, 4-96) days. Twenty-seven procedures were performed in the 20 patients. Surgical closure was undertaken in 14 patients and contraindicated in eight, six of whom underwent percutaneous closure; the other two, after reconsideration, proceeded to surgical closure. No procedural complications occurred with percutaneous closure. Percutaneous closure patients were older than surgical patients (75 vs. 64 years; P=0.01) and had a higher mean logistic EuroSCORE (87% vs. 67%; P=0.02). Rates of residual shunt and mortality did not differ between surgical and percutaneous patients (P=0.12 and 0.3, respectively). Those who underwent early VSD closure (<21 days after myocardial infarction) had higher rates of residual shunt (P=0.09) and mortality (P=0.01), irrespective of closure strategy. The mortality rate was also higher after early percutaneous closure (P=0.001), but not after early surgery. Finally, predicted mortality (logistic EuroSCORE) was higher than hospital mortality (≤30 days) in our patient population (75% vs. 30%; P=0.01). CONCLUSIONS Vigorous pursuit of closure of post-myocardial infarction VSD with a sequential surgical and/or percutaneous approach is recommended for improved outcomes.