Ventricular septal perforation (VSP) is a serious complication associated with acute myocardial infarction (MI). The purpose of this study was to investigate the determinants of in-hospital death in patients with postinfarction VSP. Between January 1990 and April 2010, we identified 37 patients from our hospital records. Univariate analysis and multivariate logistic regression analysis were performed to find the determinants of in-hospital death. In-hospital mortality was 35% (13/37 patients). History of hypertension (P = 0.03), percutaneous coronary intervention (P = 0.04), and preoperative percutaneous cardiopulmonary support (P = 0.04) were associated with in-hospital death, whereas history of hyperlipidemia was associated with in-hospital survival. The interval from MI to VSP in survivors was significantly longer than that in nonsurvivors (P < 0.01). In multivariate logistic regression analysis, a shorter interval from MI to VSP (odds ratio 0.57, 95% confidence interval 0.34-0.95, P = 0.03) was found to be an independent predictor of in-hospital death. In conclusion, in-hospital mortality was high in patients with postinfarction VSP. A shorter interval from MI to VSP was a significant independent predictor of in-hospital death.