© 2020 Belgian Society of Cardiology.Introduction: The signal peptide-CUB-EGF domain-containing protein-1 (SCUBE1) is a recently available biomarker which is expressed by activated and adhered platelets. In present study, we aimed to investigate the association between SCUBE1 levels and thrombus burden in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI). Methods: A total of 88 patients who were diagnosed with STEMI and underwent PPCI were prospectively included between July 2019 and August 2019. Blood samples were collected for routine biochemistry and serum SCUBE1 levels before PPCI and antiplatelet therapy. Angiographic coronary thrombus burden was classified based on thrombolysis in myocardial infarction (TIMI) thrombus grades. We formed two groups based on the thrombus grade: 37 (42%) patients had high thrombus burden whereas 51 (58%) patients had low thrombus burden. Results: The mean age of study population was 58.2 ± 11.8 years (34% female). The mean peak troponin I level, SCUBE1 level, SYNTAX score, and pain-to-balloon time were significantly higher in the high thrombus burden group compared to the low thrombus burden group (p <.05, for all). In ROC analysis, SCUBE1 level >65.63 ng/dL had a sensitivity of 91.9% and a specificity of 76.6% to predict high thrombus burden (AUC: 0.9256; p <.001). In multivariate analysis, SCUBE1 level (HR: 1.133, p =.004) and troponin (HR: 1.002; 95% CI 1.001–1.004, p =.003) were independent predictors of high thrombus burden. Conclusion: In the present study, we showed that SCUBE1, a novel platelet-endothelial adhesion molecule and a marker of platelet activation, is an independent predictor of high thrombus burden in patients with STEMI.