Background Reduced kidney function is common among patients with heart failure. In patients with heart failure and/or kidney disease, iron deficiency is an independent predictor of adverse outcomes. In the AFFIRM-AHF trial, patients with acute heart failure with iron deficiency treated with intravenous ferric carboxymaltose demonstrated reduced risk of heart failure hospitalization, with improved quality of life. We aimed to further characterize the impact of ferric carboxymaltose among patients with coexisting kidney impairment. Methods The double-blind, placebo-controlled AFFIRM-AHF trial randomized 1132 stabilized adults with acute heart failure (left ventricular ejection fraction <50%) and iron deficiency. Patients on dialysis were excluded. The primary end point was a composite of total heart failure hospitalizations and cardiovascular death during the 52-week follow-up period. Additional end points included cardiovascular hospitalizations, total heart failure hospitalizations, and days lost to heart failure hospitalizations or cardiovascular death. For this subgroup analysis, patients were stratified according to baseline eGFR. Results Overall, 60% of patients had an eGFR <60 ml/min per 1.73 m² (the lower eGFR subgroup). These patients were significantly older, more likely to be female and to have ischemic heart failure, and had higher baseline serum phosphate levels and higher rates of anemia. For all end points, event rates were higher in the lower eGFR group. In the lower eGFR group, the annualized event rates for the primary composite outcome were 68.96 and 86.30 per 100 patient-years in the ferric carboxymaltose and placebo arms, respectively (rate ratio, 0.76; 95% confidence interval, 0.54 to 1.06). The treatment effect was similar in the higher eGFR subgroup (rate ratio, 0.65; 95% confidence interval, 0.42 to 1.02; P _interaction = 0.60). A similar pattern was observed for all end points (P _interaction > 0.05). Conclusions In a cohort of patients with acute heart failure, left ventricular ejection fraction <50%, and iron deficiency, the safety and efficacy of ferric carboxymaltose were consistent across a range of eGFR values. Clinical Trial registry name and registration number Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency (Affirm-AHF), NCT02937454.