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Angina pectoris and abnormally slow contrast propagation into the unobstructed coronary artery, the so-called coronary slow flow (CSF) phenomenon was first recognized four decades ago but the etiology remained unclear. We reported a case of CSF phenomenon presenting with acute coronary syndrome in a middle-aged man who had multiple coronary risk factors. Intracoronary ultrasound revealed no significant plaque burden in related epicardial arteries. The pathogenic mechanisms of small artery disease and the role of endothelial dysfunction are discussed and relevant literature has been reviewed.