Background Bleeding is the major noncardiac adverse consequence of treatment in patients with non-ST-elevation (NSTE) acute coronary syndromes (ACS). The aims were to identify predictors of major bleeding in patients with NSTE ACS and to evaluate in-hospital and 1-year outcomes. Methods We evaluated 5842 patients with NSTE-ACS included in the multicenter Canadian ACS Registries. Results Patients with in-hospital major bleeding (n = 79, 1.4%) were older (75 vs 66 years, P<.001), with higher baseline creatinine (1.17 vs 1.02 mg/dL, P <.002), more diabetes (36% vs 25%, P =.04), hypertension (73% vs 54%, P <.002), previous stroke (20% vs 9%, P <.002), Killip class >= II (P <.01), and ST-depression (37% vs 18%, P <.001). Antiplatelet/ thrombotic therapies did not differ between patients with and without major bleeding. Crude event rates were significantly higher in patients with major bleeding: in-hospital death 19.2% vs 1.5% (P<.001), myocardial infarction (MI) 15.4% vs 3.8% (P <.001), and death or MI 26.9% vs 4.9% (P <.001). One-year event rates were also higher: death 35.9% vs 7.4% (P <.0001), MI 15.6% vs 6.2% (P =.0021), and death or MI 40.6% vs 12.6% (P <.0001). In multivariable analysis, independent predictors for major bleeding were age (OR 1.03, 95% Cl 1.03-1.09), hypertension (1.72, 1.0-2.97), previous stroke (1.84, 1.0-3.37), and in-hospital catheterization (1.93, 1.06-3.53) or bypass surgery (2.18, 1.0-4.76). Major bleeding was an independent predictor of 1-year death (OR 3.92, 2.07-7.41) and death or MI (2.51, 1.41-4.48). Conclusions In patients with NSTE-ACS, major bleeding is associated with increased short- and long-term rates of death and MI, and is predicted by simple clinical characteristics.