The impact of the anatomic characteristics of coronary stenoses on the development of future coronary thrombosis has been controversial. This study aimed at identifying the anatomic and flow characteristics of left anterior descending (LAD) coronary artery stenoses that predispose to myocardial infarction, by examining angiograms obtained before the index event. We identified 90 patients with anterior ST-elevation myocardial infarction (STEMI) for whom coronary angiograms and their reconstruction in the three-dimensional space were available at 6 to 12 months before the STEMI, and at the revascularization procedure. The majority of culprit lesions responsible for STEMI occurred between 20 and 40 mm from the LAD ostium, whereas the majority of stable lesions not associated with STEMI were found in distances >60 mm (p < 0.001). Culprit lesions were significantly more stenosed (diameter stenosis 68.6 ± 14.2% vs 44.0 ± 10.4%, p < 0.001), and significantly longer than stable ones (15.3 ± 5.4 mm vs 9.2 ± 2.5 mm, p < 0.001). Bifurcations at culprit lesions were significantly more frequent (88.8%) compared with stable lesions (34.4%, p < 0.001). Computational fluid dynamics simulations demonstrated that hemodynamic conditions in the vicinity of culprit lesions promote coronary thrombosis due to flow recirculation. A multiple logistic regression model with diameter stenosis, lesion length, distance from the LAD ostium, distance from bifurcation, and lesion symmetry, showed excellent accuracy in predicting the development of a culprit lesion (AUC: 0.993 [95% CI: 0.969 to 1.000], p < 0.0001). In conclusion, specific anatomic and hemodynamic characteristics of LAD stenoses identified on coronary angiograms may assist risk stratification of patients by predicting sites of future myocardial infarction.