P2Y 12 receptor antagonists act on platelet P2Y 12 receptor and inhibit platelet aggregation, which mainly prevent and treat thrombosis in patients with cardiovascular diseases. As one of the priority drugs in dual antiplatelet therapy, clopidogrel is limited by its variability in efficacy due to CYP2C19 genetic polymorphism, interactions with proton pump in hibitors (PPIs), and delayed onset. Recently, some new P2Y 12 receptor antagonists such as prasugrel and ticagrelor have been introduced in clinic. Several large-scale clinical trials have evaluated their efficacy and safety. In this review, we examined differences between new P2Y 12 receptor antagonists and clopidogrel in terms of their pharmacology, pharmacokinetics, efficacy and safety, and discussed their clinical application, providing reference for rational drug use in clinic.