Aims The incidence of infusion-related reactions during intravenous iron administration may differ between different iron formulations, but risk factors remain poorly characterised. This study aimed to compare the rates of infusion reactions in patients receiving ferric derisomaltose (FDI) compared to ferric carboxymaltose (FCM), as well as across different dilutions of FDI. Methods This was a single tertiary centre retrospective matched cohort study of patients who received FDI or FCM between January 2022 to May 2023. Reactions were classified as Fishbane or hypersensitivity and characterised by severity using the Ring and Messmer classification. Results 660 patients (330 age- and sex-matched patients who received FDI and FCM, respectively) were included. Hypersensitivity reactions occurred in 34/330 (10.3%) patients receiving FDI infusions compared to 8/330 (2.4%) patients receiving FCM (OR 4.62 [2.10-9.78], p <0.0001). All reactions to FCM and FDI were classified as mild to moderate except one grade III reaction to FDI. There was no difference in the rate of reaction between patients receiving FDI diluted in 100mL (18/165) compared to 250mL (16/165) sodium chloride (OR 1.14 [0.55–2.27], p=0.86). A history of a reaction to an alternative iron formulation was associated with increased risk of infusion reactions (OR 3.55 [0.67-18.97], p=0.14) and increasing age was associated with reduced risk (0.96 [0.94-0.99], p=0.02). Conclusions Patients receiving FDI had a significantly higher risk of mild infusion reactions compared to those receiving FCM, with no difference across different dilution volumes of FDI.