Background To investigate the significance of echocardiography combined with N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels in the evaluation and prognosis of diastolic heart failure (DHF). Methods Clinical data were collected from 168 patients with DHF. Serum levels of NT-pro BNP were first measured by ELISA. Meanwhile, the echocardiography was used to examine left ventricular end-diastolic diameter (LVEDD), left ventricular diameter (LVD), and other parameters. Multivariate logistic regression analysis was performed for variables in heart failure assessment grade or poor prognosis. Finally, the predictive ability for New York Heart Association (NYHA) class as well as prognosis was assessed by ROC curves. Results NT-pro BNP was the overexpression in the serum of patients with DHF. And the degree of elevation was related to NYHA class, while NT-pro BNP levels were significantly higher in the P-MACE group than in the N-MACE group. According to the multivariate logistic regression analysis, the ratio of peak velocity of left atrial early diastolic blood flow to early diastolic peak velocity of mitral annulus (E/Ea) and serum NT-pro BNP level was risk factors for NYHA class and prognosis. However, LVEF, LVEDD, and flow propagation velocity (Vp) can be a benefit condition. In addition, ROC curve showed that echocardiography combined with NT-pro BNP content had higher accuracy in NYHA class and prognostic assessment of DHF than applied separately. Conclusions The diagnosis of echocardiography combined with NT-pro BNP levels has the potential to distinguish the NYHA class in heart function of patients with DHF and determine the prognosis of patients.