Left main (LM) coronary disease, carotid artery disease, and peripheral arterial disease each reflects advanced atherosclerosis. The frequency of their coexistence in the same patient has not been fully elucidated. All coronary angiograms obtained at the Cleveland Clinic from November 2003 to October 2005 were analyzed for presence of LM stenosis > or =50%. Patients with previous coronary artery bypass graft surgery were excluded. Patients with available carotid ultrasound and ankle-brachial indexes formed the analysis cohorts. A total of 10,298 coronary angiograms were obtained in 9,715 patients. There were 186 patients with LM disease and 1,913 patients without LM disease with carotid artery ultrasound data. There were 29 patients with LM disease and 604 patients without LM disease with available ankle-brachial indexes. Patients with significant LM disease more frequently had associated carotid stenosis > or =60% compared with patients without LM disease (31.2% vs 15.2%, p <0.0001). Patients with LM disease had lower mean ankle-brachial indexes compared with patients without LM disease (0.78 vs 0.87, p = 0.042). In conclusion, compared with patients without LM disease, patients with LM disease have a higher burden of advanced atherosclerosis as evidenced by a higher prevalence of significant carotid stenosis and lower ankle-brachial indexes.