PROJECT SUMMARY Accumulating evidence from clinical trials suggests that a restrictive transfusion strategy is safe in most clinical settings. However, a low oxygen carrying capacity from moderate anemia may be deleterious in patients with cardiac ischemia. The potential for harm associated with anemia in patients with acute symptomatic coronary disease is supported by pathophysiological data that maintaining higher hemoglobin levels could benefit the ischemic heart by increasing oxygen delivery. Furthermore, results of the 110 patient MINT pilot trial found that all-cause mortality at 30 days was less frequent with a liberal transfusion strategy, 1 patient (1.8%), compared with a restrictive transfusion strategy, 7 patients (13.0%), (p=0.032). Systematic reviews of clinical trials evaluating transfusion strategies in patients with known ischemic heart disease document the absence of high quality data which has resulted in an ongoing controversy. The lack of high quality evidence to guide transfusions in patients with acute myocardial infarction has been cited in several major guidelines as well as by an NIH expert panel. Despite this, blood transfusions are being used as a negative indicator of quality of care by major organizations driving the adoption of restrictive strategies. The potential for adverse outcomes is real and immediate. In this multicenter pragmatic trial, we will activate 40 clinical centers and will randomly allocate 3500 patients at risk of myocardial ischemia with acute myocardial infarction and hemoglobin concentration less than 10 g/dL to be treated either according to a restrictive or liberal blood transfusion strategy. Our Primary Aim will be to determine whether a liberal transfusion threshold strategy (10 g/dL) is superior and will result in lower rates of either all cause mortality or acute myocardial infarction within 30 days following randomization as compared with a restrictive transfusion threshold strategy (8 g/dL). Our secondary aims will examine the effect of a liberal transfusion strategy compared with a restrictive transfusion strategy on adverse outcomes of transfusion related to volume overload, thrombotic risk and modified immunity. We will compare 30-day rates of congestive heart failure, thromboembolism, and pneumonia. We will also compare rates of 30-day death, myocardial infarction, and unscheduled revascularization, as well as hospital length of stay, and readmission to the hospital. We will contact the patients at 6 months to determine if the early effects on mortality are sustained or possibly enhanced. Relevance MINT is positioned to determine the threshold for blood transfusions in patients with acute myocardial infarction to minimize death and subsequent heart attacks. Given the high incidence of acute ischemic heart disease, the results of MINT can shape clinical practice.