Several studies have produced estimates of the outcome of percutaneous coronary intervention (PCI) in the field of left main (LM) coronary artery disease, but no research has been found that surveyed the issue of a comprehensive knowledge of LM anatomy and assessed the impact of different anatomic phenotypes on the likelihood of developing complications after LM PCI. We sought to develop a specific investigation on the basis of the regional anatomy and quantitative analysis of a large series of angiograms performed in our institution. We reviewed the baseline selective digital coronary angiographic examinations of 1,000 patients who did not undergo LM PCI and 296 patients with significant LM stenosis who did undergo PCI. All patients in both groups underwent a comprehensive qualitative and quantitative assessment of LM anatomical features according to several parameters. Hierarchical cluster analysis (HCA) was used to identify different anatomic phenotypes of the LM coronary artery. Three different anatomical patterns were identified by HCA. The proportion of patients with LM disease increased across clusters (19% in cluster 1, 27% in cluster 2 and 44% in cluster 3, p < 0.001). No differences were observed in terms of 18-month major adverse cardiac event-free survival among patients with LM disease undergoing PCI stratified by clusters (log rank p = 0.77). In conclusion, LM phenotypes can be identified that are more likely to present with atherosclerotic disease and significant stenosis.