Fc gamma receptor IIA could influence atherogenic processes through the production of superoxide anions, cytokines, and proteolytic enzymes as well as by oxidation of lipoproteins and enhancement of foam cell formation. In this study, we performed an interaction analysis between FCGR2A polymorphisms and ischemic stroke using direct DNA sequencing after the selection of Fc gamma receptor IIA gene based on genome-wide association study. Four of the FCGR2A polymorphisms, rs7511868 [odds ratio (OR) = 3.21; P = 0.027], rs6427595 (OR = 3.12; P = 0.008), rs7512140 (OR = 5.71; P = 0.002), and rs6696854 (OR = 3.65; P = 0.004) were significantly associated with ischemic stroke. These four polymorphisms still showed significant association after stratification analysis using the Mantel-Haenszel method. In the multivariate logistic regression, the adjusted OR estimates for rs6427595, rs7512140, and rs6696854 were 3.04 (P = 0.016), 4.84 (P = 0.015), and 3.80 (P = 0.006), respectively. The diplotype consisting of two homozygous haplotypes (H2 = AAAC) was significantly associated with ischemic stroke (OR = 17.39; P < 0.001). These results suggest that FCGR2A polymorphisms may be associated with a genetic susceptibility to ischemic stroke in a Korean population.