Oral iron is a standard treatment of iron deficient anemia despite high rates of intolerance and nonadherence and may not replenish iron stores rapidly enough to meet ongoing losses [1]. Intravenous (IV) iron has advantages but remains underutilized. Whereas most formulations of IV iron require multiple doses for replacement, low molecular weight iron dextran (LMW ID) may be administered as a total dose infusion, typically over a 4to 6-hr period [2,3]. A 4-hr infusion for doses up to 4 g was standard in our practice until 2 years ago. However, clinical studies suggest that 1 g of IV iron is an adequate dose for many patients [3–5], and it became apparent that we were frequently infusing doses of at least 1 g in 1 hr without evidence of significant adverse events [3]. Now, our clinical practice routinely infuses 1 g of LMW ID in 250 mL normal saline over 1 hr without premedication as our standard practice. We summarize our experience with the safety and efficacy of this method of administering IV iron in unselected patients with iron deficiency. From July 11, 2008 to February 25, 2010, a total of 396 consecutive iron deficient patients received 1g LMW ID infusions. The mean age was 50.7 years (range 14 to 90), 84.1% were women, 75.1% were white, and 14.4% had multiple documented drug allergies at baseline. The most common diagnoses were heavy uterine bleeding among women (43.5%) and gastrointestinal bleeding among men (33.3%). The majority (78.9%) included in this study had baseline transferrin saturation (TSAT) 20% (mean: 11.5 ± 8.7%) and serum ferritin 100 ng/mL (median: 11.0 ng/mL, range: 2) drug allergies and an increased likelihood of an AE [odds ratio (OR) 5 3.40; 95% CI: 1.09–10.63; P 5 0.036] when controlling for race, gender, and relative dose [estimated body surface area (BSA)] (Figure 2; Supplemental Table II, available online). However, this finding should be interpreted with caution due to the very low absolute incidence rate. Other variables, including baseline iron status and age, were not associated with the incidence of observed AEs. Premedication with 125mg of IV methylprednisolone was administered to only 10 patients with a history of multiple drug allergies (4), asthma, active inflammatory bowel disease, and/or a previous reaction to IV iron. Three received granisetron premedication due to anticipatory nausea (n 5 2) or nausea with prior IV iron therapy (n 5 1). All premedicated patients subsequently received the infusion without AEs. No patient received premedication with antihistamines. Clinically significant hypophosphatemia, defined as a serum phosphate level 20% and/or serum ferritin >100 ng/mL. There was no significant difference in magnitude of Hb response between these two subsets (mean difference in Hb increase between patients with TSAT 20% and serum ferritin 100 ng/mL and the others was 0.3 g/dL; 95% CI:20.0 to 0.5 g/dL; P 5 0.08). When baseline TSAT 20% and serum ferritin 100 ng/mL, 54% of infusions led to an increase in Hb of at least 1 g/dL, while 37% of infusions when TSAT >20% or serum ferritin >100 ng/mL achieved an increase in Hb of at least 1 g/dL (Supplemental Table IV, available online). A total of 31 infusions in 43 women with pregnancy-related anemia (second and third trimester, or postpartum), for whom follow-up data were available, were included in the efficacy analysis. In this subgroup, the mean change in Hb from baseline was 1.2 g/dL (95% CI: 0.79–1.65 g/dL; P 2 g/dL. Four of the patients with pregnancy-related anemia reported AEs. One resolved with a decreased rate and temporary interruption of the infusion and three received treatment with IV methylprednisolone. Although oral iron is a convenient and inexpensive therapy for iron deficient anemia, it has several important limitations. Even in patients who are not inflamed, and therefore have no problems with absorption, effective treatment requires a long course to correct anemia and completely replenish stores. Significant nonadherence and intolerance abound. While any of the available IV irons can infrequently cause acute reactions, the incidence and severity of these reactions are far less than perceived [6]. Whereas LMW ID, iron sucrose, ferric gluconate, and ferumoxytol can be administered safely and effectively, only LMW ID can be used to provide total dose repletion in a single setting (a method of administration approved in Europe but not the United States). This method of administration has typically been 2–6 hr in published reports. In some studies, doses of 3 g (and up to 4.5 g) were infused. Numerous clinical studies suggest that 1 g is an adequate dose for the majority of patients, and several support the use of 1 g/hr, providing a rationale for administering 1 g over 1 hr in this study [3,7–11]. No prospective study has shown benefit of premedication with antihistamines, yet they are often administered empirically. A study of 135 iron deficient patients who received antihistamines before the administration of IV iron reported that the most frequent AE observed was sedation due to the antihistamine [1]. Antihistamines have been associated with flushing, hypotension, supraventricular tachycardia and somnolence, all of which may be misinterpreted as iron-related reactions. In contradistinction to the AEs just described, there is a syndrome occurring in 1:200 patients described by Fishbane, consisting of arthralgia and myalgia of the chest or flank, usually Letters