Abstract. Objective. The authors tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure (CHF) and iron deficiency. Background. Anemia is common in heart failure. Iron metabolism is disturbed, and administration of iron might improve both symptoms and exercise tolerance. Methods. The authors randomized 35 patients with CHF (age 64±13 years, peak oxygen consumption [pVO 2 ], 14.0±2.7 mL/kg/min) to 16 weeks of intravenous iron (200 mg weekly until ferritin >500 ng/mL, 200 mg monthly thereafter) or no treatment in a 2:1 ratio. Ferritin was required to be <100 ng/mL or 100 to 300 ng/mL with transferrin saturation <20%. Patients were stratified according to hemoglobin levels (<12.5 g/dL [anemic group] vs 12.5–14.5 g/dL [nonanemic group]). The observer‐blinded primary end point was the change in absolute pVO 2 . Results. The difference (95% confidence interval [CI]) in the mean changes from baseline to end of study between the iron and control groups was 273 (151–396) ng/mL for ferritin ( P <.0001), 0.1 (−0.8 to 0.9) g/dL for hemoglobin ( P =.9), 96 (−12 to 205) mL/min for absolute pVO 2 ( P =.08), 2.2 (0.5–4.0) mL/kg/min for pVO 2 /kg ( P =.01), 60 (−6 to 126) sec for treadmill exercise duration ( P =.08), −0.6 (−0.9 to −0.2) for New York Heart Association (NYHA) functional class ( P =.007), and 1.7 (0.7–2.6) for patient global assessment ( P =.002). In anemic patients (n=18), the difference (95% CI) was 204 (31–378) mL/min for absolute pVO 2 ( P =.02), and 3.9 (1.1–6.8) mL/kg/min for pVO 2 /kg ( P =.01). In nonanemic patients, NYHA functional class improved ( P =.06). Adverse events were similar. Conclusions. Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients.— Okonko DO, Grzeslo A, Witkowski T, et al. Effect of intravenous iron sucrose on exercise intolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC‐HF: a randomized, controlled, observer‐blinded trial . J Am Coll Cardiol. 2008;51:103–112 .