In this study, we investigated the association of G protein beta3 subunit gene (GNB 3) C825T polymorphism with ischaemic stroke and its subtypes in the Chinese Han population in a large case-control study. A total of 990 ischemic stroke patients and 1124 controls were recruited from six medical centres in China. Genotype was determined by polymerase chain reaction and restriction fragment length polymorphism (RFLP) assay. Logistic regression analysis was performed to identify the independent risk factors for stroke. The frequency of 825T carriers is significantly higher in cerebral thrombosis in male subjects (OR=1.35, 95% CI, 1.01-1.82, P=0.046). After further adjustment with traditional risk factors to stroke, the association is not significant. In conclusion, the GNB3 825T allele is not an independent risk factor to ischaemic stroke in the Chinese population.