P atients with unprotected left main coronary artery (ULMCA) disease are considered at highest-risk of adverse cardiovascular events and mortality within the broad range of risk for patients with obstructive coronary artery disease (CAD). On the basis of several clinical and anatomic characteristics and patient/physician preference, individual patients with ULMCA disease might be treated with percutaneous coronary intervention (PCI), coronary-artery bypass grafting (CABG), or medication alone.1 Depending on the specific index treatment strategy, accurate knowledge of the key determinants of adverse cardiovascular events and mortality would be extremely useful for clinical and investigational purposes. To date, several scoring systems have been developed for risk stratification and decision making of optimum revascularization strategy in patients with complex CAD with or without ULMCA disease.2-5 However, easy application of these scoring systems in clinical practice might be hampered because of limited clinical performance and complexities. In particular, Background-Identifying predictive factors for major cardiovascular events and death in patients with unprotected left main coronary artery disease is of great clinical value for risk stratification and possible guidance for tailored preventive strategies. Methods and Results-The Interventional Research Incorporation Society-Left MAIN Revascularization registry included 5795 patients with unprotected left main coronary artery disease (percutaneous coronary intervention, n=2850; coronaryartery bypass grafting, n=2337; medication alone, n=608). We analyzed the incidence and independent predictors of major adverse cardiac and cerebrovascular events (MACCE; a composite of death, MI, stroke, or repeat revascularization) and all-cause mortality in each treatment stratum. During follow-up (median, 4.3 years), the rates of MACCE and death were substantially higher in the medical group than in the percutaneous coronary intervention and coronary-artery bypass grafting groups (P<0.001). In the percutaneous coronary intervention group, the 3 strongest predictors for MACCE were chronic renal failure, old age (≥65 years), and previous heart failure; those for all-cause mortality were chronic renal failure, old age, and low ejection fraction. In the coronary-artery bypass grafting group, old age, chronic renal failure, and low ejection fraction were the 3 strongest predictors of MACCE and death. In the medication group, old age, low ejection fraction, and diabetes mellitus were the 3 strongest predictors of MACCE and death. Conclusions-Among patients with unprotected left main coronary artery disease, the key clinical predictors for MACCE and death were generally similar regardless of index treatment. This study provides effect estimates for clinically relevant predictors of long-term clinical outcomes in real-world left main coronary artery patients, providing possible guidance for tailored preventive strategies. Clinical Trial Registration-URL: https://clinicaltrials.gov. Un...