Little is known about the usefulness of evaluating cardiac neurohormones in patients undergoing transcatheter aortic valve implantation (TAVI). The objectives of this study were to evaluate the baseline values and serial changes of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) after TAVI, its related factors, and prognostic value. A total of 333 consecutive patients were included, and baseline, procedural, and follow-up (median 20 months, interquartile range 9 to 36) data were prospectively collected. Systematic NT-proBNP measurements were performed at baseline, hospital discharge, 1, 6, and 12 months, and yearly thereafter. Baseline NT-proBNP values were elevated in 86% of the patients (median 1,692 pg/ml); lower left ventricular ejection fraction and stroke volume index, greater left ventricular mass, and renal dysfunction were associated with greater baseline values (p <0.01 for all). Higher NT-proBNP levels were independently associated with increased long-term overall and cardiovascular mortalities (p <0.001 for both), with a baseline cut-off level of ∼2,000 pg/ml best predicting worse outcomes (p <0.001). At 6- to 12-month follow-up, NT-proBNP levels had decreased (p <0.001) by 23% and remained stable up to 4-year follow-up. In 39% of the patients, however, there was a lack of NT-proBNP improvement, mainly related to preprocedural chronic atrial fibrillation, lower mean transaortic gradient, and moderate-to-severe mitral regurgitation (p <0.01 for all). In conclusion, most patients undergoing TAVI presented high NT-proBNP levels, and a lack of improvement was observed in >1/3 of the patients after TAVI. Also, higher NT-proBNP levels predicted greater overall and cardiac mortalities at a median follow-up of 2 years. These findings support the implementation of NT-proBNP measurements for the clinical decision-making process and follow-up of patients undergoing TAVI.