Introduction: Among the genetic factors for coronary artery diseases, PAI-1 4G/5G and ACE I/D polymorphisms can be noted. This study was carried out to investigate the association of these two polymorphisms and their synergism in coronary artery disease (CAD) from a sample of the Iranian population. Materials and methods: Sixty-one patients with a history of CAD and 92 healthy controls participated in our study. After DNA extraction from leukocytes, PCR was performed to characterize PAI-1 4G/5G and ACE I/D polymorphisms, using an amplification refractory mutation system technique. Results: In the studied patients, PAI-1 polymorphisms were 24.6%, 45.9%, and 29.5% for 4G/4G, 4G/5G and 5G/5G, respectively; the values for controls were 20.7%, 42.2% and 37.0%. The distribution rates of genotypes I/I, I/D and D/D in patients accounted for 29.5%, 45.9% and 24.6%; in the control group these figures were estimated to be 40.2%, 40.2% and 19.6%. Conclusion: Single and multivariate analyses showed a significant difference for the conventional risk factors, including hypertension, diabetes, hyperlipidemia, smoking and family history, for CAD between patients and controls (p value 0.001). However, no significant correlation was demonstrated considering ACE and PAI-1 polymorphisms either in association with 4G/4G or D/D genotypes or a combination of them in the Iranian population in the current study.