Background: In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger-level lower than by guidelines from The European Society for Vascular Surgery. Restricting RBC transfusion may affect blood O2 transport with a risk for development of tissue ischaemia and postoperative complications. Methods: In a single-centre, open-label, assessor blinded trial, 58 vascular surgical patients (> 40 years of age) awaiting open surgery of the infrarenal aorta or infrainguinal arterial bypass surgery undergo a web-based randomisation to one of two groups: perioperative RBC transfusion triggered by hb < 8 g/dl or hb < 9.7 g/dl. Administration of fluid follows an individualised strategy by optimising cardiac stroke volume and near-infrared spectroscopy determines tissue oxygenation. Serious adverse event rates are: myocardial injury (troponin-I ≥ 45 ng/l or ischaemic electrocardiographic findings at day 30), acute kidney injury, death, stroke and severe transfusion reactions. A follow-up visit takes place 30 days after surgery and a follow-up of serious adverse events in the Danish National Patient Register within 90 days is pending. Discussion: This trial is expected to determine whether a RBC transfusion triggered by hb < 9.7 g/dl compared with hb < 8 g/dl results in adequate separation of postoperative hb levels, transfusion of more RBC units and maintains a higher tissue oxygenation. The results will inform the design of a multicentre trial for evaluation of important postoperative outcomes.