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Objective: The purpose of this investigation was to characterize clinical variables and angiographic distribution of coronary atherosclerosis to classify patients with de novo left main (LM) disease in a real-world population presenting for coronary angiography. Background: Limited quantitative and angiographic published data exist that provide detailed quantitative information to classify potential target population for elective LM percutaneous coronary intervention (PCI) and guide development of dedicated LM PCI platforms. Methods: Medical history and clinical presentation were prospectively collected on 177 consecutive patients with LM stenosis ≥50% by coronary angiography. Blinded quantitative coronary angiography (QCA) was performed on all LM stenoses to classify LM-A (ostial), LM-B (nonostial, non-bifurcation), and LM-C (bifurcation involvement). QCA was performed on the left anterior descending (LAD), left circumflex (LCx), and right coronary arteries (RCA) and branches (≥2.5 mm) to identify lesions with ≥60% stenosis or occlusion. Results: No differences in baseline clinical history or presentation discriminated the distribution patterns of LM stenosis. QCA revealed 66% of LM stenoses were LM-C. Mean LM reference vessel diameter was 4.65 mm and average lesion length was 11.12 mm. Around 88.7% of patients had at least one lesion ≥60% in a major epicardial artery and 32.2% of patients had RCA chronic total occlusion. Right-to-left coronary collateralization was only identified in patients with obstructive stenosis in the LAD or LCx in addition to the LM stenosis. Conclusion: Dedicated LM stent platforms may need to be developed to accommodate larger vessel size and bifurcation distributions. A majority of patients with LM stenosis will require adjunctive epicardial vessel PCI to achieve complete anatomic revascularization.