Response variability to antiplatelet treatment has been described and the widespread use of acetylsalicylic acid (ASA) and clopidogrel requires clarification of the residual platelet reactivity (RPR). Various glycoprotein Ia (GpIa) polymorphisms have been investigated, but their influence on platelet reactivity in myocardial infarction (MI) patients undergoing percutaneous coronary intervention (PCI) on dual antiplatelet treatment is not still elucidated. Aim of this study was to evaluate the effect of C807T, G873A and T837C polymorphisms of GpIa on modulating platelet function in MI patients on dual antiplatelet treatment undergoing PCI. We measured platelet function by both a point-of-care assay (PFA100) and platelet-rich-plasma aggregation in 289 MI patients undergoing PCI and receiving dual antiplatelet treatment. Our data show that C807T/G873A polymorphisms, but not T837C, are associated with higher platelet reactivity. Carriers of the 807T/873A allele had significantly higher platelet aggregation values after arachidonic acid (AA) and collagen stimuli and, even if they did not reach the statistical significance, after 2 and 10 microM ADP stimuli; 807T/873A allele carriers had also significantly shorter closure times on PFA100/epinephrine membranes. At the multiple analyses, C807T/G873A polymorphisms resulted an independent risk factor for RPR defined by both AA induced platelet aggregation (OR=3.0, 95%CI 1.17-7.89, p=0.022) or by PFA100/epinephrine (OR=4.1, 95%CI 1.53-10.89, p=0.005). In conclusion, this study shows the 807T/873A allele of the GpIa gene is an independent risk factor for the RPR on dual antiplatelet treatment, and extends, in a larger acute coronary syndrome population, the observation that the 807T/873A allele is associated with higher platelet reactivity.