Iatrogenic major bleeding occurs in 4% of non–ST-segment elevation acute coronary syndromes (NSTE-ACS), causing increased in-hospital mortality. Prevention requires risk stratification based on advanced age, female sex, a history of bleeding, and renal failure (plasma creatinine, creatinine clearance). Particular caution is required in securing vascular access for percutaneous coronary interventions in high-risk patients. Use of the radial approach and of vascular sealing or suturing devices when performing a femoral approach markedly reduce the incidence of complications. Doses of heparin should be significantly reduced when combined with glycoprotein IIb/IIIa receptor inhibitors, and aspirin should be reduced to 75 to 150 mg/day when combined with clopidogrel. Such precautions should largely eliminate major bleeds in NSTE-ACS...