Aims: In heart failure (HF) iron deficiency (ID) is frequently observed and represents a major mortality risk factor. Purpose of this study was to evaluate the correlation between mortality and ID in a cohort of 661 consecutive patients hospitalized for HF worsening. Methods and results: Patients were grouped: (i)according to presence(+)/absence(-) of anaemia (A) and ID defined following World Health Organization (WHO) and European Society of Cardiology (ESC)-American College of Cardiology/American Heart Association/HF society of America (ACC/AHA/HFSA) definitions, respectively: Group A-ID- (n = 123), Group A+ID- (n = 80), Group A+ID+ (n = 247), and Group A-ID+ (n = 211); (ii) according to presence of absolute (serum ferritin < 100μg/L) and functional ID [ferritin between 100 and 300μg/L and transferrin saturation (TSAT) < 20%]; and (iii) according to TSAT <20% and ≥20%. Groups were not different for several clinical features but age, gender, kidney function, and chronic obstructive pulmonary disease. Average follow-up was 1.94 year (±420 days). Overall 5 years mortality rate was 29.5%. Only anaemia and functional ID but not ID as defined by guidelines showed an impact on prognosis. Transferrin saturation <20% (n = 360) patients showed worst prognosis compared to TSAT ≥20% (n = 301) patients. In addition, functional ID patients showed worse prognosis compared patients with ferritin <100μg/L and TSAT <20% or ≥20% likely due to more severe chronic inflammatory status [C-reactive protein, 7.4 (interquartile range 2.7-22.6) and 3.2 (1.4-8.7) mg/L, P < 0.0001 respectively]. Conclusion: We confirmed that in HF anaemia is associated to a poor prognosis. Moreover, we showed that patients with TSAT <20% had worse prognosis compared to those with TSAT ≥20% but the composite of ferritin between 100 and 300 μg/L and TSAT <20% identifies HF patients with the poorest survival rate.