Although thinning of the ventricular wall due to infarct expansion (septal aneurysm) may contribute to ventricular septal rupture (VSR), spatial factors predisposing to this mechanical complication have not been fully demonstrated. To identify the morphologic predictors of VSR, a retrospective postmortem study was performed on 17 hearts with acute anteroseptal myocardial infarction, comprising 7 with VSR and 10 without rupture. Infarct size and the extent of wall thinning were quantified. Wall thinning was defined as a decrease of less than 50% of thickness of the noninfarcted wall. The total infarct size did not differ among the groups. In the free wall (FW), the infarct was smaller in hearts with VSR than in those with a ruptured FW (p<0.05) or no rupture (p<0.01). The septal involvement was more extensive in patients with VSR than in those with FW rupture (p<0.05). Septal thinning was more extensive in hearts with VSR than in those with FW rupture (p<0.05) or non-rupture (p<0.05). A combination of a small infarct of the FW and a large septal infarct may contribute to the formation of septal aneurysm, which is believed to predispose to VSR. The presence of a small infarct of the anterior septum may be another setting for postinfarction septal rupture.