Although blood transfusion has an established place in the conventional management of acute upper gastrointestinal (GI) hemorrhage, there is growing evidence of adverse side effects of transfusion, both acute and later. An Ovid Medline literature search was performed to evaluate the significance and importance of these effects. Evidence of impaired hemostasis with repletion of blood volume in the acute phase was found in multiple studies and in uncontrolled studies in combat casualties. There are multiple large studies of a so-called immunosuppressive effect of transfused blood leading to increased infection rates and mortality dependent both on dose and on the age of the stored blood. In view of evidence of increased bleeding with early blood volume restoration and the growing evidence of so-called immunosuppressive effects of stored blood, there is a need to consider trials using a conservative utilization of blood in acute GI bleeding.