Abstract Background Anemia is a significant comorbidity in heart failure (HF), influencing patient prognosis and quality of life. In patients with HF, fluctuations in anemia status can markedly impact long-term outcomes. Purpose The aim of this study was to evaluate the long-term prognosis of HF patients according to change in anemia status at the baseline and one-year follow-up. Methods Data were obtained from a multicenter cohort of patients hospitalized for acute heart failure (AHF) from 10 tertiary university hospitals between March 2011 to February 2014. Out of 5,625 AHF patients, the study population was consisted of 1,798 patients with available data on hemoglobin levels at baseline and one-year follow-up. Anemia is defined as hemoglobin levels below 13 g/dL for men and 12 g/dL for women. These patients were then categorized into four groups: group ‘anemia to anemia’; group 2 ‘no-anemia to anemia’; group 3 ‘anemia to no-anemia’; group4 ‘no-anemia to no-anemia’. Primary outcome was the composite incidence of cardiac death or HF readmission. Results Among 1,798 patients, 718 patients (39.9%) died during follow-up (mean 1169.1 ± 880.7 days, median 1057.5 days) and 816 patients (45.4%) developed primary outcome. The patients with baseline anemia had a worse clinical profile than those without anemia. The development of primary outcome tended to significantly decrease from group 1 to group 4 (55.6% vs. 48.1% vs. 40.2% vs. 36.3%, p for trend <0.001). In addition, the incidence of all-cause death, cardiac death, readmission due to cardiac cause, and HF readmission also tended to decrease significantly toward group 4. The cumulative cardiac death or HF readmission free survival rate showed significantly lowest in the group 1 (log-rank p-value < 0.001), and the survival rate increased from Group 1 to Group 4 (Figure). After adjusting for confounding factors, Cox regression analysis showed that anemia to anemia group was independently associated with a 1.368-fold increased risk of primary outcome compared to no-anemia to no-anemia group during follow-up (Hazard ratio [HR] 1.368, 95% confidence interval [CI] 1.110-1.701, p = 0.005). No-anemia to anemia group had also a 1.376-fold increased risk of primary outcome (HR 1.376, 95% CI 1.043-1.814, p = 0.024) compared with no-anemia to no-anemia group. Conclusions In conclusion, the risk of adverse clinical outcomes including cardiac death and HF readmission increased progressively in groups transitioning from no-anemia to anemia or consistently remaining anemic in AHF patients. Conversely, those who improved from anemia to non-anemia or remained non-anemic exhibited a decreased risk, highlighting the critical role of anemia status as a determinant of long-term prognosis. Clinicians should actively manage and monitor anemia as an essential component of treatment strategies to improve long-term outcomes in patients with HF.Kaplan-Meier Survival curve