- Background Current risk assessment of patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) may fail to identify some patients with severe coronary artery disease (CAD). We aimed to identify predictors of the angiographic extent and severity of CAD in patients with NSTE-ACS undergoing early angiography and to evaluate its impact on prognosis. Methods We evaluated 923 patients with NSTE-ACS who underwent coronary angiography. High-risk coronary anatomy (HRCA) was defined as left main disease > 50%, proximal LAD lesion > 70%, or 2- to 3-vessel disease involving the LAD. Clinical characteristics, in-hospital, and 30-day outcome and 1-year mortality were compared between the high-risk (N = 370) and the low-risk groups (N = 553). Results Proportion of patients with elevated cardiac biomarkers was similar in both groups. The presence of peripheral vascular disease (OR = 1.88, 95% confidence interval [CI] = 1.62–5.80, P < 0.001) and a GRACE score of >140 (OR = 1.88, 95% CI = 1.29–2.75, P < 0.001) were the strongest predictors of HRCA. Patients with HRCA were prone to more complications during hospitalization and at 30 days (11.9% vs. 6%, P < 0.01) and increased 1-year mortality (6.7% vs. 0.9%, P < 0.001). HRCA was the strongest predictor for 30-day MACCE (OR = 2.32, 95% CI = 1.42–3.79, P < 0.001). HRCA (OR = 8.36, 95% CI = 1.01–69.4, P = 0.049; OR = 3.64, 95% CI = 1.2–11.07, P = 0.02) and GRACE score of >140 (OR = 6.86, 95% CI = 1.68–27.9, P = 0.007; OR = 4.84, 95% CI = 1.74–13.5, P = 0.002) were significant predictors of 30-day and 1-year mortality, respectively. Conclusions HRCA is predicted by clinical parameters and was not associated with elevated cardiac biomarkers. These patients fared worse when compared with those with low-risk anatomy. We suggest that HRCA predictors should be included in the risk stratification of patients with NSTE-ACS. © 2013 Wiley Periodicals, Inc.