AbstractSerum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) testing is recommended in the patients with heart failure (HF). We hypothesized that NT-pro-BNP, in combination with other clinical factors in terms of a novel NT-pro BNP-based score, may provide even better predictive power for in-hospital mortality among patients with HF. A retrospective study enrolled adult patients with hospitalization-requiring HF who fulfilled the predefined criteria during the period from January 2011 to December 2013. We proposed a novel scoring system consisting of several independent predictors including NT-pro-BNP for predicting in-hospital mortality, and then compared the prognosis-predictive power of the novel NT-pro BNP-based score with other prognosis-predictive scores. A total of 269 patients were enrolled in the current study. Factors such as “serum NT-pro-BNP level above 8100 mg/dl,” “age above 79 years,” “without taking angiotensin converting enzyme inhibitors/angiotensin receptor blocker,” “without taking beta-blocker,” “without taking loop diuretics,” “with mechanical ventilator support,” “with non-invasive ventilator support,” “with vasopressors use,” and “experience of cardio-pulmonary resuscitation” were found as independent predictors. A novel NT-pro BNP-based score composed of these risk factors was proposed with excellent predictability for in-hospital mortality. The proposed novel NT-pro BNP-based score was extremely effective in predicting in-hospital mortality in HF patients.