Metabolic syndrome (MS) is caused by genetic and environmental factors, thromboxane A synthase 1 (TBXAS1) gene polymorphism is associated with metabolic disease. This study would explore the relationship between TBXAS1 gene polymorphism and MS. A total of 3072 eligible subjects were obtained, of which 1079 cases were normal controls, 1993 cases were MS patients. subjects were followed up for 5 years and the endpoint events were recorded. The gene polymorphism of TBXAS1 was detected by using Sequenom MassARRAY methods. The results showed that significant differences were observed in ischemic stroke and the genotypes of NC_000007.14:g.139985896C>T (all P < 0.05). The incidence of ischemic stroke was significantly higher in T allele carriers than in C allele carriers (all P < 0.05). C allele was the protective factor of the onset of ischemic stroke. The interaction effects showed there were negative interactions between C allele and waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), TG, HDL-C and FPG; These findings suggest that NC_000007.14:g.139985896C>T was related to the incidence of ischemic stroke in the whole and MS population, individuals who carry the C allele have a reduced risk of stroke.