Objective To observe the clinical efficacies of ticagrelor and clopidogrel and investigate their correlation with CYP2C19 gene polymorphisms. Methods A total of 450 hospitalized patients with acute coronary syndrome in our department from March 2013 to March 2014 were recruited in this study. According to their treatment regimes, the patients were randomly divided into the ticagrelor group (n＝227) and the clopidogrel group (n＝223). Their incidence of the major adverse cardiac events (MACE) was compared in the 6 months’ follow-up. The patients were also assigned into 2 subgroups according to their carrying CYP2C19*2/*3 loss-of-function allele or not. The incidence of the MACE and bleeding events were compared between the subgroups in the follow-up. Results Between the ticagrelor group and clopidogrel group, the incidence of MACE was 8.4% and 8.2% respectively for the non-carriers of CYP2C19*2/*3 loss-of-function allele, though without significant difference (P＞0.05), and was 9.1% and 15.2% separately for the carriers, with obvious difference (P＜0.01). However, there was no statistical difference in the incidence of bleeding events between the ticagrelor and clopidogrel groups and between the carriers and non-carriers (P＞0.05). Conclusion Ticagrelor is superior to clopidogrel in decreasing the risk of MACE in the patients with acute coronary syndrome, which may be associated with carrying CYP2C19 loss-of-function allele or not.