AIM: To study the effect of of intracoronally targeted recombinant human urokinase combined with percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) with high thrombus burden. METHODS: In this retrospective analysis study, 85 AMI patients with heavy thrombus burden admitted to Wuhu Second people's Hospital for percutaneous coronary intervention (PCI) from November 2020 to November 2022 were divided into observation group (n=37) and control group (n=48) according to different treatment methods.Recombinant human urokinase were used for coronary intervention in observation group. The control group was not treated with recombinant human urokinase. The myocardial injury markers troponinI (cTnI) and creatine kinase (CK) within 24 h after PCI, the percentage of segment resolution≥50% 1 h after PCI, intraoperative coronary lesions blood flow, the incidence of adverse cardiovascular events (MACE) during hospitalization,and cardiac function index ［left ventricular end diastolic (LVED), fractional shortening (FS), left ventricular ejection fraction (LVEF) level change one month discharge were compared between the two groups after PCI.RESULTS: After PCI, the levels value of cTnI and creatine kinase in the observation group at within 24 h after PCI were (69.35±16.31) ng/mL vs. (80.52±15.20) ng/mL, (3 136.27±1 952.52) U/L vs. (4 554.51±1 982.34) U/L, which were significantly lower than those in the control group (P<0.05); the postoperative TIMI blood flow level 3 was significantly higher than that in the control group (P<0.01), the percentage of segment resolution ≥50% 1 h after PCI were significantly higher than those control group (P<0.01); Comapared with control group, the the level of LVEF was[ (54.27±4.21)% vs. (48.20±3.12)%, FS[(29.21±2.10)% vs. (21.52±1.80)%], which were significantly higher than that in the control group at one month discharge (P<0.05); which was significantly lower than that in the control group at one month discharge, LVED[(47.27±4.15) mm vs. (56.67±4.30) mm ](P<0.05). There was no significant difference in the incidence of coronary vascular disease (MACE) between the two groups (P>0.05)．CONCLUSION: Intracoronally targeted application of recombinant human urokinase combined with percutaneous coronary intervention (PCI) has a significant effect on AMI with heavy thrombus burden, which can effectively improve cardiac function, coronary blood flow and myocardial reperfusion, and reduce myocardial damage without increasing the risk of MACE．