This learning activity educates nurses in acute care settings about the causes, consequences, and evidence-based prevention of ABO and Rh blood type incompatibility errors related to transfusions. It covers the immunologic mechanisms of these life-threatening reactions as well as system and human factors, like failure to verify patient identity or follow safety protocols, that contribute to incompatible blood being administered. Statistics on transfusion-related mortality are provided. Based on established guidelines from reputable bodies like AABB and ISBT, key safety recommendations focus on strict adherence to patient ID verification, specimen collection and handling protocols, visual checks to match blood products prior to infusion, and independent double checks at the bedside along with close monitoring for signs of reactions. Specific tips for nurses aim to promote competency with identification procedures, transfusion administration safeguards, and swift intervention when suspected reactions occur to avoid dire outcomes.