Objective: To assess the anatomic characteristics of the left main coronary artery (LM), and the relation between anatomic and clinical factors and the LM bifurcation angle (BA) using a novel, three dimensional quantitative coronary angiography (3D QCA) software. Background: Percutaneous intervention of the LM is a therapeutic option in selected patients with coronary artery disease (CAD). The anatomic features of the LM and its BA are determinants of procedural success and clinical outcome. However, those features and the factors that may affect the LM BA have not been fully described. Methods: The LM anatomy was evaluated from angiograms of 203 patients (age = 66 ± 11 years, 31% female) with and without LM CAD using 3D QCA analysis (IC-PRO, Paieon, Israel). LM size as well as the proximal BA (between LM and LCX) and the distal BA (between left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX)) were measured in end-diastole. Angiographic and clinical findings were also recorded. Results: 133/203 patients (65%) had no LM CAD. 3D QCA analysis demonstrated significant variability in the anatomy of the normal LM, including the LM branch vessels (LAD, LCX) diameter, and the LM BA. Among the 70 patients with LM CAD, 44 had distal LM disease. Importantly, patients with distal LM CAD had narrower proximal BA and a wider distal BA. Multivariate analysis (adjusted for clinical and anatomic variables) identified female sex (P = 0.02), trifurcation anatomy (P = 0.009), age > 75 years (P = 0.0009), and LM length > 12 mm (P = 0.001) as independent associates of the proximal BA. Independent associates of the distal BA were: trifurcation anatomy (P = 0.001), LM length > 12 mm (P < 0.0001), age > 75 years (P = 0.004), and a history of coronary bypass surgery (P = 0.04). Conclusions: The current study demonstrates significant variability in the anatomy of the LM. The LM BA differs between patients with and without distal LM CAD, and both anatomic and clinical factors may affect the LM BA. Our findings also emphasize the possible usefulness of 3D QCA in the assessment of the LM. © 2012 Wiley Periodicals, Inc.