Glycoprotein IIIa (GpIIIa), a platelet protein that mediates platelet aggregation and thrombus formation, has attained recent widespread interest following a report that a common genetic variant of GpIIIa, known as Pla2, is an inherited risk factor for the development of premature coronary artery disease (CAD). We determined the frequency of the Pla2 allele in 589 prospectively recruited subjects aged <50 years presenting with symptomatic CAD with or without myocardial infarction and documented by coronary angiography (group I), 207 subjects investigated prospectively for restenosis 6 months after coronary balloon angioplasty (group II), and 570 control subjects without a history of angina or myocardial infarction, randomly selected from the community. Detection of the Pla2 allele was based on MspI digestion of polymerase chain reaction (PCR) amplified deoxyribonucleic acid (DNA) spanning the Pla1/a2 locus. The accuracy of genotyping was verified with a second independent method based on BstXI digestion of DNA amplified with mutagenic PCR primers. The frequency of the Pla2 allele was similar (p >0.1) in group I (170 of 1,178, 14%), group II (49 of 414, 12%), and control subjects (160 of 1,140, 14%). Among group I subjects, there was no relation (p >0.1) between the Pla2 allele frequency and the number of coronary vessels with >50% diameter obstruction, and current or previous myocardial infarction; among group II subjects, there was no difference between those with and without restenosis after angioplasty (26 of 242 and 23 of 172, respectively, p >0.1). We conclude that the Pla2 allele is not associated with a significantly elevated risk of premature CAD, myocardial infarction, or restenosis after coronary angioplasty.