Baseline, clinical, and angiographic features of 1014 Coronary Artery Surgery Study (CASS) registry patients with combined proximal left anterior descending and proximal left circumflex coronary disease were examined to define determinants of prognosis in this clinical high-risk patient subset. A stepwise Cox regression analysis identified congestive heart failure score, left ventricular contraction score, mitral regurgitation, age, and digitalis usage as independent variables predictive of 8-year survival. When patients were stratified by left ventricular contraction score, the 8-year survival rate was 62%, 49%, and 19%, respectively, for patients with a left ventricular score of 5 to 9, 10 to 14, and greater than or equal to 15 (p less than 0.0001). The presence of a stenosis greater than or equal to 70% in the right coronary artery was associated with worse survival (47% versus 54% at 8 years; p = 0.051). In conclusion, the diagnosis of combined proximal left anterior descending and left circumflex coronary artery disease represents a large prognostic spectrum that needs to be considered when counselling individual patients.