Increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration predicts poor prognosis of non-CNS cancer patients. We evaluated the association of NT-proBNP concentration with disease severity, discharge outcomes and prognosis of patients undergoing craniotomy for brain tumor. From January, 2010 until September, 2011 two-hundred and forty-five patients (age 55.05 ± 14.62 years) admitted for brain tumor surgery were evaluated for NT-proBNP serum concentration. Outcome at hospital discharge was evaluated with the Glasgow Outcome Scale (GOS). Most common diagnoses were meningioma (37%) and high-grade glioma (20%). Greater NT-proBNP concentration was associated with lower Barthel index (rho = -0.305, p = 0.001) and Mini Mental State Examination scores (rho = -0.314, p = 0.001) and with greater Hospital Anxiety and Depression scale Depression score (rho = 0.240, p = 0.026). Greater admission NT-proBNP concentration was associated with lower discharge GOS score after adjusting for patient age, gender and histological brain tumor diagnosis (β = -0.253, p < 0.001). Greater NT-proBNP concentration was also associated with greater 5-year mortality risk (HR = 1.845; 95%CI [1.166-2.920], p = 0.009) controlling for patient age, gender, history of cardiovascular disease, histological diagnosis and adjuvant therapy. In sum, greater pre-operative NT-proBNP concentration is associated with worse health status, unfavorable discharge outcome and shorter survival of brain tumor patients.