The clinical significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing left ventricular assist device (LVAD) implantation is not fully explored. NT-proBNP concentrations are influenced by body composition, renal function and intracardiac pressures; dynamic measures pre- and post-LVAD implantation. We sought to identify the individual contribution of cardiac and extracardiac factors to NT-proBNP concentrations in advanced heart failure patients before and after LVAD implantation. We retrospectively collected data from 63 patients implanted with a LVAD with NT -proBNP measurements (2006–2019). Hemodynamic measurements were obtained through right heart catheterization (RHC). Univariable linear regression and multivariable stepwise regression models were used to analyze variables associated with NT-proBNP concentrations in the pre- and post-LVAD setting. Paired t-test was performed on a subpopulation of 13 patients with complete data. We found significant differences in all extracardiac (BMI, creatinine, eGFR) and all invasive hemodynamic measurements pre-LVAD compared to post-LVAD. NT-proBNP decreased by 83 %, in the subpopulation of 13 patients: 736 pmol/L [IQR 498–1330] to 126 pmol/L [IQR 74.8–241.7]. In multivariable analysis, only creatinine remained significantly associated with NT-proBNP before LVAD implant (p = 0.016), whereas pulmonary capillary wedge pressure (PCWP) was the only independent variable associated with NT-proBNP after LVAD implant (p < 0.0001). Creatinine and PCWP were the only independent factors associated with NT-proBNP concentrations before and after LVAD implantation, respectively. Invasive hemodynamic measurements were more closely associated with NT-proBNP concentration after LVAD than extracardiac factors and reversely pre-LVAD, suggesting that NT-proBNP serves as a useful biomarker of cardiac conditions post-LVAD implantation.