Advances in antithrombotic and antiplatelet therapies have led to a reduction in ischemic event rates in percutaneous coronary intervention (PCI), acute coronary syndromes (ACS), and ST-segment elevation myocardial infarction (STEMI) but have generally resulted in an increased risk of hemorrhagic complications. In these settings, both baseline anemia and acute hemorrhage occur with relative frequency and are associated with increased morbidity and mortality. Although commonly treated with blood transfusion, this intervention may accentuate rather than attenuate both short-term and long-term risk. This review discusses the pathophysiology of anemia and the impact of anemia and transfusion on morbidity and mortality in PCI, ACS, and STEMI.