AbstractObjectivesWe sought to determine risk factors for iv iron infusion‐related reactions (IRR), and identify strategies for iron repletion after IRR.MethodsWe conducted a retrospective chart review of patients treated in the classical hematology clinic at Yale Cancer Center (n = 330 consecutive patients) from 2016 to 2021, who received iv ferumoxytol (60.3%), iron sucrose (14.8%), or iron dextran (10.9%).ResultsThe iv iron IRR was noted in 58 (17.6%) patients, 62.1% of whom had previously tolerated iv iron. The severity of IRR was mild in 22, moderate in 23, and severe in 11 patients. Most (72.4%) patients who experienced IRR tolerated a subsequent iv iron infusion. On multivariable analysis, a history of non‐medication allergies was associated with greater odds of IRR (odds ratio [OR] 2.12, 95% confidence interval (CI): 1.16–3.87, p = .01). No patients with type AB blood, and few with type A blood (n = 6), had IRR; compared to type A or AB together, patients with type B (OR 5.00, 95% CI: 1.56–16.06, p = .007) or type O (OR 3.71, 95% CI: 1.44–9.55, p = .007) blood had greater odds of IRR.ConclusionsThis study highlights a possible association of blood type with iv iron IRR; prospective studies with larger patient numbers are warranted to explore this association.