Aim: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR2285, the first oral coagulation factor XIa (FXIa) inhibitor developed in China in combination with aspirin, clopidogrel or ticagrelor in healthy subjects. Methods: This study was a single-center, randomized, double-blind, placebo-controlled (only SHR2285) design. A total of 52 healthy subjects, 29 male and 23 female, were enrolled in this study. The subjects were divided into three groups: A, B and C, 16 subjects in group A (aspirin+clopidogrel+placebo or SHR2285 200mg bid (1:3)), 16 subjects in group B (aspirin+clopidogrel+placebo or SHR2285 300mg bid (1:3)) and 20 subjects in group C (aspirin+ticagrelor+placebo or SHR2285 300mg bid (2:3)), respectively. All groups were administered orally for 6 consecutive days. Results: 1. SHR2285 was well tolerated, and all adverse events were mild. There was no evidence of an increased risk of bleeding. 2. After 6 days of twice-daily administration, SHR2285 could reach a steady state. The half-life of SHR2285 was 13.9h, 14.5h and 13.8h respectively. 3. SHR2285 markedly inhibited FXI: C and prolonged APTT. The maximum inhibition rates of FXI: C in the three groups were 84.8%, 89.3% and 92.2% and the maximum prolongation time of APTT was 2.08-, 2.36-, and 2.26-fold, respectively. 4. The combination of aspirin, clopidogrel or ticagrelor had limited effect on the AUC of SHR2285. Conclusion: These data suggest that SHR2285, a potential oral FXIa inhibitor, is expected to become a novel, safe and effective anticoagulant.