Background Compared to clopidogrel, Ticagrelor significantly reduces the risk of cardiovascular events in patients with acute myocardial infarction(AMI) however increases the incidence of bleeding and the risk of fatal intracranial hemorrhage. In this study, we screened the AMI patients with clopidogrel resistence, and determined whether ticagrelor sequential therapy could reduce the risk of cardiovascular events and bleeding risk.Methods A total of 319 AMI patients were enrolled in this prospective clinical study. The platelet inhibition rates in adenosine 5’-diphosphate(ADP) pathways were measured by a thrombelastography(TEG) system. The patients with clopidogrel resistance were divided into Ticagrelor sequential therapy group(ticagrelor for 3months and clopidogrel for 9 months, n=143) and Clopidogrel group(clopidogrel for 12 months, n=176). The risk of major adverse cardiac events(MACE) and the safety end points at 1-year follow-up were analyzed.Results The rates of stent thrombosis(ST)(2.1% vs. 8.0%, P=0.017)or MI(2.8% vs. 10.2%, P=0.009)were lower in the ticagrelor sequential therapy group than in the clopidogrel group. Dyspnea was more often in the ticagrelor sequential therapy group than in the clopidogrel group(17.5% vs. 4.5%, P<0.001). No significant difference in the rate of major bleeding was found between the groups(3.4% vs. 3.9%, P=0.528). Conclusions In AMI patients with hyporesponsiveness to clobidogrel ticagrelor sequential therapy group significantly decreased the rates of ST and MI without increased risk of major bleeding as compared with clopidolgrel. Background Compared to clopidogrel, Ticagrelor significantly reduces the risk of cardiovascular events in patients with acute myocardial infarction (AMI) however increases the incidence of bleeding and the risk of fatal intracranial hemorrhage. In this study, we screened the AMI patients with clopidogrel resistence, and determined whether ticagrelor sequential therapy could reduce the risk of cardiovascular events and bleeding risk. Methods A total of 319 AMI patients were enrolled in this prospective clinical study. The platelet inhibition rates in adenosine 5’-diphosphate (ADP) pathways were measured by a thrombelastography (TEG) system. The patients with clopidogrel resistance were divided into Ticagrelor sequential therapy group (ticagrelor for 3months and clopidogrel for 9 months, n = 143) and Clopidogrel group (clopidogrel for 12 months, n = 176). cardiac events (MACE) and the safety end points at 1-year follow-up were analyzed. Results The rates of stent thrombosis (ST) (2.1% vs. 8.0%, P = 0.017) or MI (2.8% vs. 10.2%, P = 0.009) were lower in the ticagrelor sequential therapy group than in the clopidogrel group. Dyspnea was more often in the ticagrelor sequential therapy group than in the clopidogrel group (17.5% vs. 4.5%, P <0.001). No significant difference in the rate of major bleeding was found between the groups (3.4% vs. 3.9%, P = 0.528). Conclusions In AMI patients with hyporesponsiveness to clobidogrel ticagrelor sequential therapy group significantly decreased the rates of ST and MI without increased risk of major bleeding as compared with clopidolgrel.