Background: Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein with inhibitory effects on the formation of plasmin from plasminogen by plasminogen activator. Thus, it prevents clot lysis in vessel walls. Several evidences prove the relationship between coronary artery disease and response to fibrinolytic therapy in patients with myocardial infarction with PAI-1 level. Opium addiction is one of the most important factors in causing myocardial infarction and cardiovascular events. This is due to it causing imbalance between coagulation and anticoagulation factors in the blood. This study was designed and implemented to determine the levels of PAI-I in opium-addicted patients with coronary artery disease in comparison with non addicts. Methods: In this case-control study, 160 patients with coronary heart disease, which was confirmed by angiography results, were enrolled. All of the patients had a medical history, their creatine levels and lipid profile were evaluated, morphine urine test was performed, and after that a blood sample was taken to determine the levels of PAI-1. Thus, the 80 patients who had a positive morphine urine test result formed the case group, and the control group was constituted of the 80 patients with negative morphine test results. The two groups were matched. Findings: Average level of PAI-1 in the control group was 2.4±2.6 and in the case group was 8.8 ± 9.1 and it was statistically significant (P < 0.001). The frequency of two vessel disease was higher in opium addicted patients than non-addicted patients and this was statistically significant (P = 0.030). However, the frequency of single vessel and three vessel disease was the same in the two groups. The two groups had no differences in age, lipid profile, and creatinine level. Moreover, females are at a higher risk of high PAI-1 levels. Conclusion: PAI-1 levels in opium addicted patients with coronary heart disease are higher than other patients. In these patients, the risk of atherosclerosis and myocardial infarction is higher than normal.