TheSERBP1gene is a well-known regulator of SERPINE1 mRNA stability and progesterone signaling. However, the chaperone-like properties ofSERBP1have recently been discovered. The present pilot study investigated whetherSERBP1SNPs are associated with the risk and clinical manifestations of ischemic stroke (IS). DNA samples from 2060 unrelated Russian subjects (869 IS patients and 1191 healthy controls) were genotyped for 5 common SNPs—rs4655707, rs1058074, rs12561767, rs12566098, and rs6702742SERBP1—using probe-based PCR. The association of SNP rs12566098 with an increased risk of IS (risk allele C;p= 0.001) was observed regardless of gender or physical activity level and was modified by smoking, fruit and vegetable intake, and body mass index. SNP rs1058074 (risk allele C) was associated with an increased risk of IS exclusively in women (p= 0.02), non-smokers (p= 0.003), patients with low physical activity (p= 0.04), patients with low fruit and vegetable consumption (p= 0.04), and BMI ≥25 (p= 0.007). SNPs rs1058074 (p= 0.04), rs12561767 (p= 0.01), rs12566098 (p= 0.02), rs6702742 (p= 0.036), and rs4655707 (p= 0.04) were associated with shortening of activated partial thromboplastin time. Thus,SERBP1SNPs represent novel genetic markers of IS. Further studies are required to confirm the relationship betweenSERBP1polymorphism and IS risk.