Purpose:: Twenty percent of patients with acute myeloid leukemia (AML) undergoing induction or reinduction chemotherapy at the University of Virginia Health System from May 2011 to August 2014 had a proven or probable invasive fungal infection (IFI). The purpose of our initiative was to reduce the percentage of proven or probable IFIs in patients with AML undergoing induction or reinduction chemotherapy at the University of Virginia Health System to 10% or less by June 2017, in concordance with national averages.Methods:: A multidisciplinary team was formed to lead the comprehensive quality improvement (QI) initiative. The team generated both current process state and ideal process state workflow diagrams, a cause-and-effect diagram, and a Pareto diagram to determine the most relevant etiology for proven or probable IFIs in patients with AML undergoing induction or reinduction chemotherapy.Results:: Analysis led to the creation of a program standardizing antifungal prophylaxis in this patient population, along with a suggested work-up for recalcitrant fevers. Through two tests of change (Plan-Do-Study-Act cycles 1 and 2), the QI initiative was able to effectively reduce the proven or probable IFI rate to 0% since program implementation in August 2016, thus surpassing both QI initiative goals and national rates of IFI. Mean length of stay (LOS) decreased by 3.4 days, and median intensive care unit LOS decreased by 2 days.Conclusion:: Creation of a standardized antifungal prophylaxis program led to a marked decrease in LOS and the proven or probable IFI rate of patients with AML undergoing induction or reinduction chemotherapy.