Platelet membrane glycoprotein IIb/IIIa plays an important role in adhesion and platelet aggregation. Polymorphisms of genes in platelet activation and fibrinolysis have been associated with myocardial infarction (MI), however this has not been confirmed by others, and results are still controversial. The aim of this study was to determine the frequency distribution and association of polymorphism in the platelet glycoprotein GPIIIa PLA/A2 and the possible interaction with the 4G/5G in the plasminogen activator inhibitor genes with ST elevation acute myocardial infarction (STEAMI) in young Mexican subjects. A total of 254 unrelated patients with first STEAMI ≤45 years of age, who were admitted to a cardiovascular intense care unit and 254 healthy controls matched by age and gender were recruited from January 2006 and May 2011. The PIA1/A2 and 4G/5G polymorphism were determined in all participants by a PCR restriction based restriction endonuclease digestion. There was a difference in the PIA2 allele distribution between both groups (P = 0.001). Also, we found an increased percent of 4G allele in the group of patients compared to control group (P = 0.001). There was an increased risk for STEAMI in carries with the allele PIA2 and 4G (OR = 4.3, CI 95 % 1.7-6.5). The modifiable risk factors such: smoking, hypertension, family history of cardiovascular disease, and dyslipidemia were associated with myocardial infarction. This is the first study to evaluate the role of gene polymorphism in both the thrombotic and fibrinolytic pathways in young Mexican individuals with STEAMI and suggest a synergistic effect between PIA2 and 4G allele.