OBJECTIVES: Chronic heart failure (CHF) is associated with poor quality of life resulting from physical and psycho-social limitations. The FAIR-HF trial showed clinical and quality of life benefits of iron deficiency treatment in CHF patients using ferric carboxymaltose (FCM), an intravenous (i.v.) iron preparation. This study evaluated the cost-effectiveness of iron repletion using FCM in CHF patients, from the perspectives of the statutory health insurance (Germany) and the National Health Service (UK). METHODS: Using data from FAIR-HF, a randomized, double-blind, controlled clinical trial (n=459), per-patient costs and clinical effectiveness of FCM were estimated. Economic assessment was based on published costs associated with New York Heart Association (NYHA) functional classes. Effectiveness was assessed as the number of QALYs gained, derived from EQ-5D scores. The ICER of FCM was determined compared to placebo. Time horizon of this within-trial analysis was 24 weeks. RESULTS: In the FAIR-HF trial, NYHA classes were significantly improved in the FCM group compared with placebo (p<0.001). Estimated per-patient costs (excluding iron costs) were €2625 and €2919 (Germany), and £4155 and £4621 (UK), for FCM and placebo arms, respectively. Based on the reimbursed price for FCM in Germany and UK (€28 and £19 per 100 mg iron) and the mean iron dosage of the clinical study (1850mg) plus administration costs, a net investment of €530 and £68 per patient would be required. FCM resulted in an estimated gain of 0.0254 QALYs over the study period. The ICER of FCM ranged from €20,872 to £2,682 per QALY gained for the FAIR-HF dosing regimen, compared to placebo. ICER-differences result from disparities in administration and medication costs.  CONCLUSIONS: From the German and UK payers’ perspective, managing iron deficiency in CHF patients using i.v. FCM can be considered cost-effective. Improved symptoms and better quality of life contribute to economic benefits seen with FCM.