Objective: Plasminogen Activator Iinhibitor-1 (PAI-1) is an endothelial enzyme secreted from the endothelial cells, smooth muscles, liver and adipocytes. PAI-1 activity in circulation is mainly determined by the endothelial cell release. PAI-1 plays a major role in inhibiting fibrinolysis rapidly by forming complexes with tissue plasminogen activator (t-PA). When bound to PAI-1, t-PA loses its function and can no longer produce cleavage of plasminogen into active form plasmin whose function to lyse the fibrin. The present study aims to determine the frequency of PAI-1 polymorphism in metabolic syndrome patients, and find a possible relation between the prothrombotic state of metabolic syndrome patients caused by high PAI-1 activity in plasma and other biochemical parameters indicating insulin resistance. Methods: This work was performed, as a case-control study on 69 patients with metabolic syndrome and 45 age- and sex-matched controls. DNA was extracted from peripheral blood of all cases and controls. DNA analysis was carried out by polymerase chain reaction (PCR) then restriction digestion of the PCR products (RFLP) for PAI-1. In addition, PAI-1 activty, leptin and insulin were measured by ELISA method while fasting blood glucose and lipid profile estimated by colorimetric method. The homeostatic model assessment-insulin resistance (HOMA-IR) index was also calculated. Results: Genotyping of PAI-1 in control group 4G/4G genotype was (27/45, 60%), 4G/5G genotype was (7/45, 15.6%) and 5G/5G genotype was (11/45, 24.4%), whereas in cases of metabolic syndrome 4G/4G genotype was (18/69, 26.1%), 4G/5G genotype was (44/69, 63.8 %) and 5G/5G genotype was (7/69, 10.1%). The plasma PAI- 1 activity, leptin levels, and HOMA-IR index were significantly higher in cases of metabolic syndrome in comparison to controls. Conclusion: We concluded that PAI-1 polymorphism play a pivotal role in the prothrombotic state in the metabolic syndrome patients.