Background: Hypoxia-inducible factor 1 (HIF-1) is a critical regulator for cellular oxygen balance. Myocardial hypoxia can induce the increased expression of HIF-1 alpha. Our goals were to evaluate the value of HIF-1 alpha in predicting death of patients with acute decompensated heart failure (ADHF) and describe the in vivo relationship between serum HIF-1 alpha and N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels. Method: We included 296 patients who were consecutively admitted to the emergency department for ADHF. The primary end point was in-hospital death. The patients were categorized as HFrEF (patients with reduced systolic function) and HFpEF (patients with preserved systolic function) groups. Results: In our patients, the median admission HIF-1 alpha level was 2.95 +/- 0.85 ng/ml. The HIF-1 alpha level was elevated significantly in HFrEF patients and deceased patients compared with HFpEF patients and patients who survived. The HIF-1 alpha level was positively correlated with NT-proBNP and cardiac troponin T levels, and negatively correlated with left ventricular ejection fraction and systolic blood pressure. Kaplan-Meier curves revealed a significant increase in in-hospital mortality in ADHF patients with higher HIF-1 alpha levels. Multivariable Cox regression analysis showed that HIF-1 alpha levels were not correlated with the short-term prognosis of ADHF patients. Conclusions: This is the first study to evaluate the circulating levels of HIF-1 alpha in ADHF patients. Serum HIF-1 alpha levels may reflect a serious state in patients with ADHF. Due to the limitations of the study, serum HIF-1 alpha levels were not correlated with the in-hospital mortality based on regression analysis. Further studies are needed to demonstrate the diagnostic and/or prognostic role of HIF-1 alpha as a risk biomarker in patients with ADHF.