Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-tumor antibiotic conjugate with proven efficacy in pediatric and adult patients with CD33+ acute myeloid leukemia (AML). Adverse effects commonly associated with GO include hyperbilirubinemia, elevated transaminases, and sinusoidal obstruction syndrome (SOS). Cardiotoxicity has not been a commonly described adverse event. We describe two pediatric patients with relapsed/refractory AML who received fractionated GO monotherapy and subsequently developed severe acute left ventricular dysfunction. Both patients achieved remission, recovered cardiac function with medical therapy, and tolerated subsequent stem cell transplantation.