Oral iron replacement is the standard therapy in iron-deficiency anemia (IDA) [1]. However, 59% of patients have gastrointestinal toxicity [2]. With impaired iron uptake from the gastrointestinal tract (in anemia of chronic disease (ACD) [3] or after bariatric surgery), suboptimal responsiveness to exogenous erythropoietin (in chronic renal failure) [4], in patients with cancer receiving chemotherapy [5], or when oral iron is poorly tolerated, IV iron therapy is the preferred mode of repletion [2,5]. Although effective in increasing hemoglobin [6][7][8][9][10], the relative safety of the available IV iron preparations is not well documented. We examined the comparative safety of IV iron formulations used at hospitals associated with our institution. Among 619 unique patients who received IV iron over a 2-year period, we found 32 adverse events (AEs), ranging from urticaria to chest pain. There were no serious AEs or anaphylactic-type reactions. In a multivariate model, there was no difference in AE rates between low-molecular-weight iron dextran (LMWD) and ferric gluconate; however, iron sucrose had significantly higher odds ratio of AEs (OR 5 5.7; 95% CI 5 1.6-21.3). Our data suggest that AE rates with IV iron are acceptable. More widespread use of LMWD, in particular, which can be given safely as a total dose infusion (TDI), should be considered.Five formulations of IV iron are approved by the United States Food and Drug Administration: LMWD (INFeD in the United States; approved at 100 mg dose), high-molecular-weight iron dextran (HMWD or Dexferrum; approved at 100 mg dose), ferric gluconate (Ferrlecit; approved at 125 mg dose, given over eight sessions for 1 g), iron sucrose (Venofer; approved at 100-400 mg dose, given in three or more sessions for 1 g), and ferumoxytol (Feraheme; approved at 510 mg dose, given in two sessions for 1 g). LMWD, although approved in the United States at 100 mg dose, can be given safely as a TDI of 1 g or more in one session.During the 2-year study period, 619 unique patients received at least one treatment cycle of IV iron. A total of 3,174 infusions of IV iron were given. The mean age of patients was 50.7 years; 81.1% were women and 70.6% were White. Four hundred seventy-eight patients (77.2%) were seen at a tertiary center and 470 (75.9%) were treated for IDA. Three hundred ninetythree patients (63.5%) received ferric gluconate, 121 patients (19.5%) received LMWD, 96 patients (15.5%) received iron sucrose, and nine patients (1.5%) received HMWD. Ferumoxytol was not used at our institution hospitals during the years of this study. A total of 32 AEs were reported in association with IV iron. AEs were seen in 14 patients who received ferric gluconate, three patients who received LMWD, 11 patients who received iron sucrose and four of those treated with HMWD (see Table I). All AEs were mild or moderate and included urticaria/rash, facial flushing, lip numbness, lightheadedness, nausea, swelling/erythema at the injection site, rigors, fevers, and chest pain (see Table II). No sever...