OBJECTIVE To investigate the association between thromboxane A2 receptor (TXA2R) gene promoter rs2271875, rs768963 polymorphism and acute cerebral infarction in Chinese Han population. METHODS A prospective study was conducted. From October 2009 to May 2013, 223 patients with cerebral infarction (cerebral infarction group) and 142 cohorts with normal physical examination results (control group) from Taizhou City Central Hospital in Zhejiang Province were enrolled. Triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were determined by enzymatic colorimetry, whereas blood glucose was determined with hexokinase. The genotypes of rs2271875 and rs768963 polymorphism in TXA2R gene were detected by the polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. Differences in gender, age, serum TG, TC, HDL-C, LDL-C, concentration of blood glucose, and blood pressure (systolic pressure, diastolic pressure) between cerebral infarction group and control group were compared as well as TXA2R promoter rs2271875, rs768963 genotype and allele frequencies distribution. RESULTS The significant differences in males (147 cases vs. 57 cases, χ(2)=23.385, P=0.000), serum TG (2.02±1.14 mmol/L vs. 1.56±0.79 mmol/L, t=4.663, P=0.000), blood glucose (6.40±2.50 mmol/L vs. 5.28±0.92 mmol/L, t=6.084, P=0.000), systolic pressure (146.64±21.34 mmHg vs. 135.73±18.09 mmHg, t=5.234, P=0.000), diastolic blood pressure (86.29±11.79 mmHg vs. 80.74±11.23 mmHg, t=4.468, P=0.000) between cerebral infarction patients and controls were found. The results from multi-logistic regression analysis suggested that male was an independent risk factor for cerebral infarction [odds ratio (OR) 3.300, 95% confidence interval (95%CI) 1.905-5.175, P=0.000]. There were statistically significant differences between infarction group and the control group both in aspects of genotype (TT: 0.112 vs. 0.183, TC: 0.498 vs. 0.535, CC: 0.390 vs. 0.282, χ(2)=6.298, P=0.043) and the allele frequency distribution (T: 0.361 vs. 0.451, C: 0.639 vs. 0.549, χ(2)=5.839, P=0.016) of TXA2R gene rs768963. No statistical significant difference was found in rs2271875 in respect of genotype (GG: 0.336 vs. 0.352, GA: 0.480 vs. 0.451, AA: 0.184 vs. 0.197, χ (2)=0.302, P=0.859) and the allele frequency distribution (G: 0.576 vs. 0.577, A: 0.424 vs. 0.423, χ(2)=0.001, P=0.974). Coefficient of both linkage disequilibrium (D') of rs2271875 and rs768963 was 0.684. When the pair was haplotype AT, the frequency in the infarction group was significantly lower than that in the control group (0.034 vs. 0.081, χ(2)=7.883, P=0.005). CONCLUSIONS rs768963 gene mutation, but not that of the rs2271875, showed significant correlation with the occurrence of cerebral infarction. There was a loose linkage disequilibrium between rs2271875 and rs768963 of TXA2R. Haplotype AT reduces the risk of cerebral infarction.