BACKGROUND AND OBJECTIVES In previous studies, researchers highlight that children have higher rates of transfusion reactions than adults. However, little is known about the pediatric populations that experience reactions, and there are no reports that consider appropriateness of pediatric transfusions in relation to preventable harm. With this study, we aim to describe pediatric transfusion reactions occurring at an academic institution and to quantify transfusion reactions that resulted from inappropriate transfusion indications, thereby identifying an area of potentially preventable patient harm (PPH). METHODS This is a case series of acute transfusion reactions in pediatric patients at a single institution from January 2018 to December 2019. We reviewed patient data, clinical documentation, and transfusion reaction reports to determine the appropriateness of transfusions and calculate PPH. RESULTS A total 155 acute transfusion reactions occurred in 106 pediatric patients, amounting to a total reaction rate of 544 of 100 000 transfusions. In 65% of reactions, the indication for transfusion was appropriate by institutional standards; 23% had questionable indication; and 12% were not indicated. The rate of potential PPH from inappropriate transfusions was 67 of 100 000 transfusions. CONCLUSIONS Transfusion reactions that occur during inappropriately ordered blood transfusions represent PPH. Efforts should be made to develop transfusion guidelines, standardize practice, and educate physicians to prevent transfusion-related harm.