Aim To investigate the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) for patients with acute coronary syndrome and high bleeding risk. Methods 108 patients with acute coronary syndrome and high bleeding risk and receiving PCI treatment were randomly divided into test group (bivalirudin group) and control group (heparin group), 54 cases in each group. TIMI blood flow, activated coagulation time (ACT), platelet count, platelet aggregation rate, high-sensitivity C-reactive protein (hs-CRP) and interleukin-4 (IL-4), 30-days bleeding events and major adverse cardiovascular events (MACE) were compared between the test group and the control group before and after operation. Results There was no significant difference in TIMI blood flow between the test group and the control group. The ACT compliance rate, platelet count, platelet aggregation rate, hs-CRP, IL-4 and other indicators in the test group were significantly better than those in the control group, and the differences were statistically significant (P＜0.05). The incidences of hemorrhagic events and MACE in the test group were significantly lower than those in the control group, and the differences were statistically significant (P＜0.05). Conclusion The application of bivalirudin during PCI for patients with acute coronary syndrome and high bleeding risk can significantly reduce the incidences of bleeding events and MACE, and has good safety.