Swine (Sus scrofa domesticus) are commonly used large animal subjects for the study of disease and preclinical therapies. Organ machine perfusion is a therapy that has gained momentum as a research platform for the study of ex vivo organ preservation and therapeutics. However, complex perfusion circuits and research protocols often require large volumes of blood as perfusate. Here, we report a technique for increasing terminal blood yield during swine organ and blood procurement; our method involves acute normovolemic hemodilution and exsanguination via the femoral artery. We collected a total of 47 ± 4 mL/kg of blood and 4.3 ± 0.6 g/kg of hemoglobin, representing 73% ± 6% of the estimated blood volume and 64% ± 8% of the total estimated intravascular hemoglobin (n = 4). Neither pH, lactate, nor pO2 levels changed significantly during blood procurement. Acute normovolemic hemodilution is an effective method for increasing RBC and hemoglobin yield during blood procurement in swine.