Background: Prevalence of Acute Myocardial Infarction (AMI) in younger age is increasing in worldwide and it has been reported that 60% of AMI in young age is due to genetic causes. SNP inPAI-1 4G/5G plays major role and there is a need to authenticate its effectiveness and sensitivity. The aim of this study is to ascertain SNP in PAI-1 (4G/5G) as an independent biochemical marker for the South Indian young AMI patient’s less than 45 yearsand to find its association with other risk factors of AMI. Methodology: This cross sectional study subjects includes40 Patients aged less than 45 years with AMI withtypical chest pain, ST Elevation in ECG and a rise in serum CK-MB, without any other known risk factorsand age and sex matched 40 control. ARMS-PCR was done with separated DNA. Remaining Serum was used to analyze Urea, HDL, CK-MB and other factors. Finally statistical analysisis done using SPSS-20.0. Result: Statistical analysis showed significant variation of SNP inPAI-1(P ≤ 0.001) between patients and controls. Further, positive significant changeswere observed between patients and controls in Serum Urea: P ≤ 0.001, Serum Glucose: P ≤ 0.04, Serum AST: P ≤ 0.001, Serum CK-MB: P ≤ 0. 001. A significant inverse association was observed in SNP of PAI-1 and Serum HDL. Conclusion: This study confirms the independent association between STEMI and the 4G/5G allele polymorphism among South Indian euthenics and an inverse association of 4G/5G polymorphism with Serum HDL-cholesterol levels.