AIMS: Our purpose was to investigate the association between the B-type natriuretic peptide (BNP) level at discharge, the occurrence of worsening renal function (WRF), and long-term outcomes in patients with heart failure (HF). METHODS AND RESULTS: We enrolled hospitalized acute HF patients. We divided patients into four groups on the basis of BNP <250 pg/mL (BNP-) or BNP ≥250 pg/mL (BNP+) at discharge and the occurrence of WRF during admission: BNP-/WRF-, BNP-/WRF+, BNP+/WRF-, and BNP+/WRF+. We evaluated the association between BNP at discharge, WRF, and cardiovascular/all-cause mortality/hospitalization due to HF. Clinical follow-up was completed in 301 patients. At discharge, percentages of the patients with clinical signs of HF were low and similar among four groups. The median follow-up period was 1206 days (interquartile range, 733-1825 days). The composite endpoint of cardiovascular mortality and HF hospitalization was significantly different between the four groups [12.9% (BNP-/WRF-), 22.7% (BNP-/WRF+), 35.8% (BNP+/WRF-), and 55.4% (BNP+/WRF+), P < 0.0001]. All-cause mortality was also different etween the four groups (15.1%, 38.6%, 28.7%, and 39.3%, respectively, P = 0.003). In the multivariate Cox proportional hazards model, the combination of BNP ≥250 pg/mL and WRF showed the highest hazard ratio (HR) for composite endpoint (HR, 5.201; 95% confidence interval, 2.582-11.11; P < 0.0001), and BNP-/WRF+ was associated with increased all-cause mortality (HR, 2.286; 95% confidence interval, 1.089-4.875; P = 0.03). Patients in BNP+/WRF+ had a higher cardiovascular mortality (28.6%), and those in BNP-/WRF+ had a high non-cardiovascular mortality (29.5%). CONCLUSIONS: Heart failure patients with BNP ≥250 pg/mL at discharge and in-hospital occurrence of WRF had the highest risk for the composite endpoint (cardiovascular mortality and HF hospitalization) among groups.