Aim To evaluate the clinical efficacy and safety of ticagrelor's antiplatelet therapy for patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing direct percutaneous coronary intervention (PCI).Methods A total of 164 patients diagnosed with STEMI who underwent direct PCI was randomly divided into two groups:ticagrelor group (40 cases) and clopidogrel group (124 cases). According to the results of platelet aggregation rate on the fifth day after treatment, clopidogrel group was divided into two subgroups:non-clopidogrel resistance (CPGR) group (81 cases) and CPGR group (43 cases). The patients in group CPGR were changed to oral administration of ticagrelor. The patients were followed up for 3 months. 5 days, 1 month, 3 months after medication, platelet aggregation rate, main adverse cardiovascular events (MACE) (including cardiac death, nonfatal myocardial infarction, stroke, revascularization of target vessels, stent thrombosis, recurrent angina pectoris, cardiac insufficiency) and adverse drug reactions (including haemorrhage and dyspnea) were analyzed and compared between ticagrelor group and non-CPGR group. Change of platelet aggregation rate before and after the change of medicine was analyzed in CPGR group. Results Platelet aggregation rates in ticagrelor group were significantly lower than that in non-CPGR group at 5 days, 1 month and 3 months after treatment (33.94%±14.90% vs 53.13%±14.07%, 25.26%±8.89% vs 35.51%±9.45%, 24.91%±7.55% vs 31.57%±9.53%), and differences were statistically significant (P＜0.05). In CPGR group, the platelet aggregation rate decreased significantly after 1 month's change to ticagrelor (28.33%±8.11% vs 64.50%±11.38%), and difference was statistically significant (t＝18.944, P＜0.05). Followed up for 3 months, the incidences of MACE and mild to moderate dyspnea in ticagrelor group were significantly lower than those in non-CPGR group, and the differences were statistically significant (P＜0.05). There was no significant difference in mild bleeding between the two groups (P＞0.05). There were no severe bleeding and severe dyspnea in the two groups. Conclusion The antiplatelet effect of ticagrelor is superior to clopidogrel, and it is safe and effective for CPGR patients with mild adverse reactions and good safety.