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Relevant studies indicate that coagulation-related genes (CGs) are associated with the development and progression of ischemic stroke (IS). This study aimed to detect differentially expressed coagulation genes in IS patients using gene sequencing technology and perform bioinformatics analysis. A comparison between the IS group and the control group revealed a total of 1,045 differentially expressed genes (DEGs), including 847 upregulated genes and 198 downregulated genes. Ultimately, four coagulation-related genes were determined. Results from the disease risk prediction model demonstrated that APBB1IP, CR1, F5, and VASP possess diagnostic value for IS. Focusing on these four key genes, we constructed a competing endogenous RNA (ceRNA) network. Furthermore, immune infiltration analysis revealed that decreases in naive CD4+ T cells and M2 macrophages, along with increases in activated memory CD4+ T cells and neutrophils, are likely involved in the pathogenesis of IS.