Background and Purpose-Platelets and components of the coagulation cascade are known to be instrumental in the pathogenesis of arterial occlusive disorders. The aim of this meta-analysis is to test the hypothesis that genetic variation in the platelet glycoprotein 1b␣ and Factor VII genes influence the occurrence of ischemic stroke. All genetic association studies that examined the R353Q (rs6046) polymorphism of the Factor VII gene and 2 polymorphisms of the platelet glycoprotein (1b␣) gene (Thr/Met rs6065 and Kozak sequence Ϫ5 C/T rs2243093) in relation to ischemic stroke were examined. Methods-Electronic databases Embase, Medline, and HuGEnet were searched for all years up until June 2006 for all studies that evaluated any of these candidate genes and stroke. Results-Pooled ORs were calculated with 95% CIs using both fixed and random effects models. Meta-analysis for Factor VII (R353Q) did not detect any effect on ischemic stroke risk. Further estimation resulted in pooled OR 1 QQ versus RRϭ0.9 (95% CI: 0.4 to 1.9) and pooled OR 2 for RQ versus RRϭ0.9 (95% CI: 0.6 to 1.4). These results were robust and homogeneous. Pooling ORs for the platelet glycoprotein 1b␣ Kozak variant Ϫ5 T/C polymorphism showed extreme heterogeneity with differing effect directions across studies. Fisher's method of pooling was therefore used to calculate a combined probability value, which was highly significant (PϽ0.001). The pooled OR for platelet glycoprotein 1b␣ Met/Met v Thr/Thr was 1.0 to 2.0, depending on the sensitivity analyses, and for Thr/Met versus Thr/Thr, the pooled OR was between 1.3 and 1.4. These results were consistent, reasonably robust, and implied a dominant genetic effect. Conclusion-This analysis provides strong evidence that the Factor VII R353Q gene polymorphism is not associated with ischemic stroke, that the Thr/Met polymorphism of GP1b␣ is associated with ischemic stroke in a dominant genetic model, and that the Kozak sequence polymorphism of GP1b␣ may be close to another causative locus that is associated with ischemic stroke. (Stroke. 2008;39:1710-1716.)