Aim To investigate the efficacy and safety of dabigatan ester in antithrombotic therapy in coronary heart disease patients with percutaneous coronary intervention (PCI) combined with atrial fibrillation and high bleeding risk. Methods A total of 140 coronary heart disease patients with PCI combined with atrial fibrillation and high bleeding risk who had been admitted to the Second Affiliated Hospital of Shenyang Medical College from May 2016 to October 2018 were enrolled. The patients were randomly divided into the dabigatan ester group and the control group. Both groups of patients were treated with triple antithrombotic drugs from the beginning of PCI to 4 weeks after surgery, and then changed to double antithrombotic drugs until 12 months after surgery, in which the dabigatan ester group was given dabigatan ester and the control group was given warfarin. The platelet count, coagulation function, liver function and rental function were compared between the two groups of patients before and after PCI. The bleeding and thromboembolic events were observed simultaneously. Results There were no significant differences in platelet count, plasma D-dimer, fibrinogen (FIB), liver function, and renal function between the two groups before and after treatment (P>0.05). Activated partial thromboplastin time (APTT) was increased after treatment in both groups. Compared with the control group, the increase of APTT after treatment was more significant in the dabigatan ester group and the difference was statistically significant(P<0.05). International normalized ratio (INR) was increased in both groups after treatment. Compared with the dabigatan ester group, the increase of INR after treatment in the control group was more significantly obvious (P<0.05), and the level of INR remained at the standard level(2.0～3.0). The incidence of bleeding events and thromboembolic events in the dabigatan ester group was significantly lower than that in the control group (P<0.05). Conclusion During the antithrombotic therapy for coronary heart disease patients with PCI combined with atrial fibrillation and high bleeding risk, antiplatelet drugs combined with dabigatan ester, compared with warfarin, can more effectively prevent thromboembolism events, and significantly reduce the incidence of hemorrhage events.