Background: As a National Cancer Institute-designated comprehensive cancer center, we manage a wide variety of patient care, from treatment to supportive measures. In the first three months of 2023, our safety event reporting software recorded 30 iron sucrose reactions, more than the three reactions reported from July to November 2022. This increase triggered our medication safety team to focus on identifying the cause of these reactions to improve patient safety. Methods: A multicenter retrospective chart review was conducted of patients who received IV iron sucrose and experienced a hypersensitivity reaction between July 2021 and March 2023 at the University of Kansas Cancer Center. The goal of the review was to identify potential risk factors for these adverse events. The chart review first investigated reaction type and symptoms, then the manufacturer, and finally the dose. Results: We identified 40 patients who experienced 44 reactions to iron sucrose from July 2021 to March 2023. Delayed reactions were observed in 68% of patients (n = 30), and 52% of patients (n = 23) had received premedication before their infusion. 25% of patients (n = 11) required an emergency department visit, and three were admitted to inpatient care. 80% of reactions (n = 35) followed a dose of iron sucrose greater than 300 mg. 60% of patients (n = 24) had previously tolerated iron infusions, with 23% (n = 9) previously receiving iron sucrose at a lower dose and 45% (n = 18) previously receiving a different iron infusion. Conclusions: We found that higher doses of iron sucrose were associated with an increased risk of reaction. Based on this finding, we proposed to our Cancer Center Medication Safety Subcommittee that a maximum dose of 300 mg should be considered for patients who receive iron sucrose infusions to improve patient safety. A rapid iterative change in dosing was implemented and has resulted in a reduction in iron sucrose reactions to previously observed numbers. This reduction in reactions further supports our initial findings and has improved patient safety across our patient care sites.