Objective To evaluate the anticoagulant efficacy and safety of bivalirudin in patients with acute coronary syndrome (ACS) and stage 4 chronic kidney disease (CKD) during percutaneous coronary intervention (PCI). Methods A retrospective analysis was made of the clinical data of 39 ACS patients with CKD stages 2 to 4 who underwent PCI in Hankou Hospital of Wuhan from April 2017 to October 2019. The patients were divided into control group (CKD stages 2 to 3) and observation group (CKD stage 4) according to the CKD clinical staging criteria. The two groups were compared for the activated clotting time (ACT) in the perioperative period, activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) at 24 h after operation, bleeding at 30 d after operation, and major adverse cardiac and cerebrovascular events (MACCE). Data were analyzed using SPSS statistics 20.0. Comparisons between groups were performed using t tests orχ² tests. Results There were no significant differences between the control and observation groups in ACT at 10 min after drug administration[(438.38±76.79) vs (413.61±66.49) s], at immediate postoperative period [(457.38±73.13) vs (425.28±60.96) s], and at 2 h after drug withdrawal [(184.21±48.15) vs (171.39±38.86) s] (P>0.05 for all). Control and observation groups did not have significant differences in APTT [(37.67±5.51) vs (39.50±9.04) s], TT [(37.52±8.21) vs (38.44±7.04) s], and PT [(14.76±3.13) vs (15.00±3.01) s] at 24 h postoperatively (P>0.05 for all). At 30-d follow-up, there was no significant difference between control and observation groups in the incidence of BARC type 1 bleeding events [14.29% (3/21) vs 11.11% (2/18)] and BARC type 2 bleeding events [4.76% (1/21) vs 5.56% (1/18)] (P>0.05 for both), and no patients had a BARC type 3 to 5 bleeding event. There was no significant difference between the two groups in the incidence of MACCE [9.52% (2/21) vs 11.11% (2/18)] (P>0.05). Conclusion Bivalirudin had good efficacy and safety in anticoagulation in patients with ACS and CKD4 during PCI.