<b><i>Objectives:</i></b> Elevated B-type natriuretic peptide (BNP) levels following acute myocardial infarction (AMI) are associated with adverse outcomes. The role of serial BNP monitoring after AMI has been poorly investigated. We aimed to evaluate the prognostic value of in-hospital serial BNP measurements in AMI patients. <b><i>Methods:</i></b> Patients with AMI (n = 1,924) were retrospectively evaluated. We selected patients with at least 2 in-hospital BNP measurements. The association between in-hospital mortality and BNP measurements (earliest, highest follow-up and the variation between measurements) were tested in multivariate models. <b><i>Results:</i></b> Serial BNP levels were determined in 176 patients. Compared to the rest of the population, these patients were older and had higher mortality rates. In the adjusted models, only the highest follow-up BNP remained associated with in-hospital death (odds ratio 1.06; 95% confidence interval, CI, 1.01-1.15; p = 0.014). Receiver-operating characteristic curve analysis demonstrated that the highest follow-up BNP was the best predictor of in-hospital death (area under the curve = 0.75; 95% CI 0.64-0.86). <b><i>Conclusions:</i></b> Serial BNP monitoring was performed in a high-risk subgroup of AMI patients. The highest follow-up BNP was a better predictor of short-term death than the baseline and in-hospital variation values. In AMI patients, a later in-hospital BNP assessment may be more useful than an early measurement.