Background: ST segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality worldwide. The development of post myocardial infarction left ventricular systolic dysfunction and heart failure is an ominous complication. Several factors play a role in the development and progression of heart failure; one of the recently studied factors is genetic polymorphism of the renin-angiotensin system. Several studies have evaluated the association of the ACE gene I/D polymorphism and various cardiovascular risk factors, especially hypertension and kidney disease. However the role of the ACE gene I/D polymorphism in the development of acute post-MI systolic dysfunction and heart failure was controversial. Aim: We sought to evaluate the associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) in patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 52 patients with STEMI (50% treated by primary PCI (26 patients] without AHF and 50% treated by fibrinolytic therapy [26 patients]) were included in the study. Serum ACE activity was measured at hospital on admission and 24 h later. ACE gene polymorphism was determined using conventional PCR method. Echocardiography was done during the index stay. Thirty apparently healthy subjects were assigned to the control group. Results: Serum ACE activity was higher in ACE DD genotype carriers when compared to ACE ID and II genotype subjects in both STEMI patients and the control group. However the difference did not reach statistical significance. Serum ACE activity on admission was significantly higher in patients with a high Killip class (p = 0.02). Serum ACE activity was significantly higher in patients whose EF(<40%) when compared with ACE activity in patients whose EF (40-54%) and further when compared with levels in patients whose EF (≥55%). Serum ACE activity showed a statistically significant negative correlation with the ejection fraction. (p = 0.04). Patients with ACE DD genotype had a higher incidence of acute heart failure compared to ACE ID/II genotypes , yet the difference was statistically insignificant (77.5 vs. 69% respectively) but with no statistical significance. There was no significant difference in the EF in both groups. (50.54±12.70 vs. 50.5±10.70 %, p=0.99). Conclusions: These results suggest that there is a significant association between the ACE activity on admission and after 24 hours and the development of acute post-MI heart failure and left ventricular dysfunction. The ACE gene I/D polymorphism has no significant association with the development of heart failure and left ventricular dysfunction post STEMI.