OBJECTIVE This study sought to evaluate short- and long-term outcomes of patients undergoing emergency percutaneous coronary intervention (PCI) for acute myocardial infarction due to a culprit lesion in an unprotected left main coronary artery. METHODS In this retrospective, 2-center, international observational study, 5,261 patients were admitted between February 2005 and December 2008 with acute myocardial infarction and treated with PCI; of these, 1,277 were ST-segment elevation myocardial infarction and 3,984 non-ST-segment elevation myocardial infarction. We identified 48 patients among this cohort who underwent emergency PCI to an unprotected left main coronary artery culprit lesion. RESULTS Mean age was 70 ± 12.5 years, and 45% of the patients presented with ST-segment elevation myocardial infarction or new left bundle branch block. Cardiogenic shock was present in 45%, and distal left main coronary artery disease was present in 71% of patients. Angiographic procedural success was achieved in 92% of patients. Overall in-hospital mortality was 21%, due in all cases to refractory, multiorgan failure. Twenty-five percent experienced major adverse cardiac events, defined as death, myocardial infarction, stent thrombosis, and target vessel revascularization. In patients presenting in cardiogenic shock, in-hospital mortality was 32%. At 1-year follow-up, in-hospital survivors had a mortality rate of 10.5%, whereas 18.4% experienced subsequent major adverse cardiac events. Long-term prognosis was excellent in hospital survivors with a 1-year survival rate of 89.5%. CONCLUSIONS Patients with acute myocardial infarction and thrombosis of the unprotected left main coronary artery are a high-risk subgroup with a substantial mortality, particularly if they present in cardiogenic shock. We demonstrate that in these patients, PCI is a feasible treatment option associated with reasonably good outcomes. Long-term prognosis is excellent in hospital survivors with an 89.5% survival rate at 1 year.