Background: The no-reflow phenomenon is a critical complication following percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), which can significantly affect morbidity and mortality. Despite advancements in interventional cardiology, no-reflow remains a challenge, with various factors contributing to its occurrence. Objective: This study aims to identify independent risk factors for the no-reflow phenomenon in STEMI patients undergoing direct PCI and to develop a practical scoring system for predicting the likelihood of its occurrence. Methods: In a retrospective cohort analysis, 1,345 patients who underwent direct PCI at a single center were evaluated. Baseline characteristics, clinical manifestations, and angiographic findings were meticulously recorded. Multivariate logistic regression was employed to ascertain independent predictors for no-reflow. The derived scoring system was based on statistically significant variables, including age, collateral circulation, thrombus burden, lesion diameter, and ACEI/ARB therapy. Results: The mean age of the development cohort (n=1011) was 61.2±11.2 years, with the validation cohort (n=334) averaging 62.1±10.8 years. No-reflow was present in 80.1% of the development group with TIMI blood flow grade 1. Independent predictors of no-reflow included age ≥55 years (OR 2.100, p=0.001), collateral circulation <grade 2 (OR 2.907, p=0.002), thrombus burden ≥4 points (OR 1.920, p<0.001), and lack of ACEI/ARB therapy (OR 1.678, p=0.017). The scoring system demonstrated a sensitivity of 42.0% and a specificity of 78.4%, with PPV and NPV of 45.8% and 78.5%, respectively. Conclusion: The study identified several key predictors for no-reflow and established a scoring system that may aid clinicians in the early identification of patients at risk for no-reflow post-PCI. This scoring system, given its simplicity and reliance on readily available clinical data, has the potential to be incorporated into routine clinical practice, subject to validation in future prospective studies.