To evaluate the association between platelet glycoprotein polymorphisms and the risks of single and second eye involvement with nonarteritic anterior ischemic optic neuropathy (NAION).Case-control study.Ninety-two consecutive patients with NAION, 26 of whom had second eye involvement, and 145 controls who attended the eye clinic for nonvascular entities.Polymerase chain reactions and restriction enzyme analyses were performed for genotyping 5 platelet glycoprotein polymorphisms on DNA extracted from whole blood.Frequencies of the various platelet polymorphisms.One of the 5 platelet glycoprotein polymorphisms analyzed, the B allele of the glycoprotein Ibalpha variable number of tandem repeats (VNTR), was a significant independent risk factor for NAION, with an odds ratio of 4.25 and a 95% confidence interval of 1.67 to 10.82 (P = 0.0026). All other platelet glycoprotein polymorphisms were similarly distributed in patients and controls. In addition, 9 of 16 patients who bore the VNTR B allele (56.3%) had second eye involvement, whereas among patients not harboring the VNTR B allele only 17 of 72 patients (23.6%) had second eye involvement (P = 0.009). Moreover, second eye involvement occurred earlier in patients who bore the specific polymorphism.The presence of the VNTR B allele of glycoprotein Ibalpha confers a significant risk for NAION and predisposes affected patients to second eye involvement.