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Background Although there is evidence that patients who experience major bleeding after an acute coronary event are at higher risk of death in the months after the event, the incidence and impact on outcome of bleeding beyond 1 year of follow-up in patients with stable coronary artery disease (CAD) are largely unknown. Objectives The goal of this study was to assess the incidence, source, determinants, and prognostic impact of major bleeding in stable CAD. Methods We prospectively included 4,184 consecutive CAD outpatients who were free from any myocardial infarction (MI) or coronary revascularization for >1 year at inclusion. Follow-up was performed at 2 years, with major bleeding defined as a type ≥3 bleed using the Bleeding Academic Research Consortium (BARC) definition. Results There were 51 major bleeding events during follow-up (0.6%/year). Most events were BARC type 3a bleeds with 12 fatal bleeds (type 5). In most cases (54.9%), the site of bleeding was gastrointestinal. Major bleeding was significantly associated with mortality (adjusted hazard ratio: 2.89; 95% confidence intervals: 1.73 to 4.83; p < 0.0001). The increased risk of bleeding associated with vitamin K antagonist (VKA) treatment was particularly evident when VKA was combined with an antiplatelet therapy (APT). In contrast, the risk of cardiovascular death, MI, or nonhemorrhagic stroke did not differ in patients who received VKA + APT versus patients on VKA alone. Conclusions In patients with stable CAD (i.e., >1 year, with no acute events), major bleeding events are rare, but such events are an independent predictor of death. When oral anticoagulation is required, concomitant APT should not be prescribed in the absence of a recent cardiovascular event. [ABSTRACT FROM AUTHOR]