To determine the prognostic importance of significant narrowings involving the proximal left anterior descending coronary artery (LAD), 866 medically treated patients with significant coronary artery disease (CAD) were followed after cardiac catheterization for a mean of 17 months (range 1 to 46). Coronary narrowings in all patients were evaluated based on site relative to large branches and on angiographic severity. Prognosis was best predicted by the presence of at least 70% diameter reductions in the LAD before the first 2 large branches (chi 2 = 16, p = 0.0001). At 3 years, there was a 94% cumulative survival rate in patients with less than 70% stenoses at this location, but an 82% survival rate in patients with 70% or more stenoses (p less than 0.0001). In addition, although the presence of proximal LAD narrowings was the best predictor of prognosis in patients with a low global ejection fraction, this was not so in patients with normal ejection fractions, as this subgroup had an excellent overall prognosis. Thus, the presence and severity of significant stenoses in the proximal LAD are stronger predictors of prognosis than stenoses elsewhere in the major coronary arteries. The presence of an angiographically significant narrowing in this anatomic location is highly correlated with an increased 1- to 3-year mortality rate.