Abstract: Ventricular Sepal Defect (VSD) remains an infrequent but a serious, devastating and life-threatening complication of Acute Myocardial Infarction (AMI); our aims were study on Post-MI VSD and identifying risk factors of mortality. forty-one patients, admitted with Post-MI VSD in Shahid Madani hospital in Tabriz from March 2000 until March 2006, assessed and correlation among mortality with age, sex, Hypertension (HTN), Hyperlipidemia (HLP), previous MI, Diabetes Mellitus (DM), renal dysfunction, respiratory disease and clinical and paraclinical findings such as vital sings and Ejection Fraction (EF) considered. Patients age was between 46- 83 year with average age of 67.6� 9.2 year. Female to male ratio was 1.05: 1 and hospital mortality was 58.5%. From 24 patients who admitted with Killip classification above two, 87.5% expired (p<0.0001). From 20 patients with cardiogenic shock, 90% expired (p<0.0001). 83.3% from 28 patients who did not operated, was dead (p = 0.02). From 21 patients with systolic blood pressure under 90 mmHg, 85.7% expired (p<0.0001). Other factors such as age, sex, previous MI, HTN, HLP, DM, renal dysfunction, respiratory disease, Congestive Heart Failure (CHF), EF, type of surgery, thrombolytic therapy, smoking, location of MI, diastolic blood pressure, size of VSD has no correlation with mortality (p>0.05). Killip Classification 3 and 4, cardiogenic shock and early surgery are the most important factors in patients` prognosis.