Despite the deleterious and sometimes catastrophic consequences of proximal left anterior descending (LAD) artery occlusion, there is a paucity of data to guide the treatment of patients with such disease. Our aim was to describe outcomes with medical therapy, angioplasty, or left internal mammary artery (LIMA) bypass grafting in patients with 1-vessel, proximal LAD disease. We retrospectively analyzed prospectively collected data from 1,188 patients first presenting only with proximal LAD disease at 1 center over 9 years. We assessed the rates of death, acute myocardial infarction, and repeat intervention by initial treatment over a median 5.7 years of follow-up. Patients undergoing angioplasty or LIMA bypass were more often men and had progressive or unstable angina; those receiving medical therapy had a lower median ejection fraction. Both revascularization procedures offered slightly better adjusted survival versus medicine (hazard ratio for angioplasty, 0.82; 95% confidence interval, 0.60 to 1.11; hazard ratio for bypass, 0.74; 95% confidence interval, 0.44 to 1.23). Bypass, but not angioplasty, was associated with significantly fewer composite end point events (death, infarction, or reintervention, p <0.0001), and angioplasty was associated with a higher composite event rate than bypass or medical therapy (p <0.0001 and p = 0.0003, respectively). The initial advantages of bypass and medicine over angioplasty diminished over time; angioplasty became more advantageous than medicine after 1 year (p = 0.05) and not significantly different from bypass. Treatment of 1-vessel, proximal LAD disease with medicine, angioplasty, or UMA bypass resulted in comparable adjusted survival. However, LIMA bypass alone reduced the long-term incidence of infarctions and repeat procedures.