Objective To investigate the clinical characteristics and coronary artery lesions of patients with ventricular septal rupture (VSR) after acute myocardial infarction (AMI) in order to provide theoretical evidence for early identification of these patients at high risk. Methods A total of 2 544 consecutive cases of AMI hospitalized in Chinese PLA General Hospital from January 1995 to January 2010 were enrolled in this study, and those having VSR were assigned into VSR group (n＝40), and 120 randomly sampled cases without VSR were assigned into control group (n＝120). Then their clinical and coronary angiographical characteristics were analyzed. Results The VSR group had significantly higher ratio of female patients (62.5% vs 36.4%, P＜0.01), and obviously older age [(66.85±10.92) vs (60.79±12.65) years, P＜0.01] than the control group. The serum levels of C-reactive protein (CRP), D-dimer, serum creatinine (SCr), and troponin T (TnT) were significantly higher, while hemoglobin (Hb), hematocrit (Hct) and red blood cells count (RBC) were obviously lower in the VSR group (P＜0.05). Conclusion Female, senior age, higher levels of CRP, D-dimer, SCr and TnT, and lower values of Hb, Hct and RBC are risk factors for VSR in AMI patients.