Brain natriuretic peptide (BNP) is used as a prognostic biomarker for patients with heart failure (HF) in clinical practice, however, the correlation between BNP levels and the prognosis of HF in patients with reserved left ventricular systolic function (RLVSF) is not clear. Thus, the aim of the present study was to evaluate the added value of BNP in the prognosis of HF patients with RLVSF. Inpatients with cardiovascular disease (mean age, 65.7 years; male, 790; female, 625) admitted to the Division of Cardiology at Jinshan Hospital of Fudan University (Shanghai, China) between June 2006 and December 2009 underwent follow-up examinations. Plasma BNP levels were analyzed and measurements of the left ventricular ejection fraction (LVEF) were performed by echocardiography. Evaluations of the patients with HF were performed according to the New York Heart Association (NYHA) classification system. The duration of the follow-up period ranged between 21 and 63 months (average duration, 35.8 months) and key events included cardiovascular mortality, readmission due to cardiovascular disease or mortality due to other reasons. Survival times decreased with increasing BNP levels in all the follow-up patients (Spearman’s ρ, −0.1877; P<0.0001). Among the 1,415 patients, 1,312 underwent echocardiographic detection. A total of 395 patients with NYHA classes II–IV and a LVEF ≥45% were selected. The incidence of compound endpoint events was significantly higher in the patients that had BNP levels of >100 pg/ml when compared with the patients that had BNP levels of ≤100 pg/ml (37.07 vs. 23.93%; relative risk, 1.55); consequently the survival times were significantly reduced (P=0.0039). A negative correlation was identified between the BNP levels and the survival times in these patients (Spearman’s ρ, −0.1738; P=0.0005). These results indicated that the levels of BNP may be used to predict the prognosis of patients with cardiovascular disease. The prognoses of patients with higher BNP levels were worse compared with the patients with lower BNP levels. Furthermore, significant correlations were confirmed in the HF patients with RLVSF.