Background:Unfractionated heparin (UFH),despite its limitations,has been used as the primary anticoagulant altative during the percutaneous coronary intervention (PCI).Some studies indicated that intravenous enoxaparin could be an effective and safe option.Our team used enoxaparin alone at one time according to the guidelines (Class ⅡA) and found a little catheter thrombosis during PCI.We recommend a new anticoagulation strategy using enoxaparin in combination with UFH.Enoxaparin has a more predictable anticoagulant response with no need of repeatedly monitoring anticoagulation during PCI.This retrospective study aimed to evaluate the efficacy and safety of using enoxaparin in combination with UFH in PCI patients with complex coronary artery disease.Methods:Between January 2015 and April 2017,600 PCI patients who received intravenous UFH at an initial dose of 3000 U plus intravenous enoxaparin at a dose of 0.75 mg/kg (observation group) and 600 PCI patients who received UFH at a dose of 100 U/kg (control group) were consecutively included in this retrospective study.The endpoints were postoperative 48-h thrombolysis in myocardial infarction (TIMI) bleeding and transfusion and 30-day and 1-year major adverse cardio-cerebrovascular events (MACCE).Results:Baseline clinical,angiographic,and procedural characteristics were similar between groups,except there was less stent implantation per patient in the observation group (2.13 vs.2.25 in the control group,P =0.002).TIMI bleeding (3.3％ vs.4.7％) showed no significant difference between the observation group and control group.During the 30-day follow-up,the rate of MACCE was 0.9％ in the observation group and 1.5％ in the control group.There was no significant difference in the rates of MACCE,death,myocardial infarction,target vessel revascularization,cerebrovascular event,and angina within 30 days and 1 year after PCI between groups as well as in the subgroup analysis of transfemoral approach.Conclusions:UFH with sequential enoxaparin has similar anticoagulant effect and safety as UFH in PCI of complex coronary artery disease.