Diffuse coronary artery disease jeopardizes myocardium, increasing surgical mortality in primary coronary artery bypass grafting (CABG). We sought to determine the impact of diffuseness on pre- and post-discharge outcomes for both primary and reoperative CABG (REOP). Using a validated system for measuring diffuseness of coronary disease, preoperative angiograms were scored for primary CABG (n=792) and REOP cases (n=268) performed 1997-2004. A diffuseness score (DS)>18 was defined as elevated. In-hospital mortality, intermediate-term survival, and in-hospital composite outcome (COMP) (one or more of: mortality, stroke, MI, deep sternal infection, sepsis, IABP insertion, or return to OR) were examined. In-hospital mortality and COMP for patients with DS>18 were significantly higher (7.9% vs 2.4%, p<0.0001), (17.8% vs 9.2%, p<0.0001). DS (mean+/-SD) was higher in REOP cases than primary CABG (18.9+/-7.1 vs 14.4+/-6.0, p<0.0001). By multivariate analysis, DS>18 (OR 2.00, 95%CI, 1.20-3.32, p=0.008) and REOP (OR 2.40, 95%CI, 1.53-3.77, p<0.0001) were independently associated with COMP. Using propensity scores 82% of cases with DS>18 (n=289) were matched 1:1 to cases with DS<or=18. In-hospital mortality and COMP were significantly higher for cases with DS>18 (6.9% vs 2.8%, p=0.02), (16.6% vs 10.4%, p=0.03). Comparing cases with DS<or=18 versus DS>18 and primary CABG versus REOP, survival at 2 years was 92.1% versus 84.5% (p=0.001) and 92.7% versus 82.7% (p<0.0001), respectively. Diffuse coronary artery disease is an important predictor of morbidity and mortality in primary and REOP CABG patients, and should be considered in both individual patient assessment and risk adjustment.