Introduction: Being a multifactorial disease, stroke is one of a major causes of death and disability worldwide. Several genetic polymorphisms have been associated with stroke etiophatology and FGB −455 G>A and GP IIIa PIA1/A2 are among them. In the present study, we investigated the association between FGB −455 G>A and GP IIIa PIA1A2 polymorphisms and the risk of ischemic stroke in a group of Romanian stroke patients. Subjects and methods: This case-control study included 148 patients with ischemic stroke and 150 healthy age, sex and ethnically matched unrelated controls. FGB −455G>A and GP IIIa PIA1A2 genotyping was carried out using PCR-RFLP. The association of FGB −455G>A and GP IIIa PIA1A2 polymorphisms and cardiovascular risk factors with ischemic stroke was tested using logistic regression analysis. Results: Molecular analysis did not reveal an increased frequency of the FGB -455 G>A variant allele and GP IIIa PIA1/A2 variant allele in the study group compared to the control group (p = 0.140, OR = 0.750, 95% CI = 0.522 - 1.077; p = 0.823, OR = 0.944, 95% CI = 0.558 - 1.599 respectively). Furthermore, after performing logistic regression analysis adjusted for the known risk factors, a positive association with stroke was found in smokers (p = 0.026, OR = 1.800, 95% CI = 1.071 - 3.024) Conclusions: No association was found between FGB −455 G>A and GP IIIa PIA1/A2 polymorphisms and ischemic stroke in the studied population.