Aim To investigate the relationship between serum signal peptide-CUB-epidermal growth factor domain containing protein 1 (SCUBE1), endothelial cell specific molecule-1 (Endocan) levels and no coronary reflow after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Methods 120 ASTEMI patients treated by emergency PCI in the Emergency Department of Sanya People's Hospital of Hainan Province were included in observation group. According to the blood flow classification of thrombolysis in myocardial infarction (TIMI) after PCI, ASTEMI patients were divided into no-reflow group and reperfusion group. Another 60 healthy subjects were selected into control group. Blood samples were collected to measure and compare the levels of serum SCUBE1 and Endocan in patients with ASTEMI before PCI, immediately after PCI, 48 hours after PCI and in control group. Multivariate Logistic regression was used to analyze the risk factors of no-reflow. ROC curve was used to analyze the clinical value of SCUBE1 and Endocan before PCI in predicting no-reflow of coronary artery after PCI. Results Compared with control group, the levels of serum SCUBE1 and Endocan in observation group were increased before PCI, immediately after PCI and 48 hours after PCI (P＜0.05). There were significant differences in left ventricular ejection fraction, proportion of history of coronary heart disease, C-reactive protein, neutrophil/lymphocyte, troponin T, time from onset to reperfusion and lesion length between no-reflow group and reperfusion group (P＜0.05). Compared with the reperfusion group, the levels of serum SCUBE1 and Endocan in no-reflow group were increased before PCI, immediately after PCI and 48 hours after PCI (P＜0.05). Multivariate Logistic regression analysis showed that the history of coronary heart disease, left ventricular ejection fraction, SCUBE1 and Endocan levels before PCI were significant factors affecting the occurrence of no-reflow of coronary artery after PCI (P＜0.05). The area under the ROC curve predicted by SCUBE1 combined with Endocan before PCI was 0.870 (95%CI:0.785～0.955). Conclusion The high serum levels of SCUBE1 and Endocan before PCI are risk factors affecting no-reflow of coronary artery after PCI in patients with ASTEMI.The combined detection of SCUBE1 and Endocan before PCI is helpful to predict the risk of no-reflow of coronary artery after PCI.