Background: B-type natriuretic peptide (BNP) is a hormone secreted by the ventricles under hemodynamic stress and congestive failure. Objective: The objective of the present study was to evaluate whether BNP can be used as a valid screening test for the presence of a hemodynamically significant patent ductus arteriosus (hsPDA) in the preterm neonate. Materials and methods: This was a prospective blinded study involving preterm neonates with birth weights ≤1500g and gestational age ≤34 weeks. Each enrolled neonate underwent the initial echocardiogram for a clinical suspicion of patent ductus arteriosus (PDA) and BNP assay within 3 hours of each other. Those neonates who did not have a PDA or who were not treated underwent a repeat echo and BNP measurement 48 to 72 hours after the first echo. In patients who received treatment for a PDA, an echo and BNP were repeated 48 to 72 hours after completion of treatment. Results: A total of 29 newborns with a median birth weight of 870g (560 to 1325g) and a median gestation of 26 weeks (24 to 31 weeks) were enrolled at a median age of 7 days (2 to 28 days). BNP levels were significantly higher in neonates with hsPDA (n = 14) compared to those without (n = 15) (508.5±618.2 vs 59.5±69.9pg/ml, p<0.005). At a cutoff value of 70pg/ml, BNP had a sensitivity of 92.9%, specificity of 73.3%, positive likelihood ratio of 3.5 and negative likelihood ratio of 0.09 for detection of hsPDA. BNP levels dropped significantly after medical or surgical closure of hsPDA (n = 12), (404.9±159.2 to 25.1±4.1pg/ml, p = 0.03). Conclusions: Elevation of plasma BNP accurately detects the presence of hsPDA in premature infants. Successful closure is reflected by a corresponding decrease in BNP. At a cutoff of 70pg/ml, BNP is a useful screening tool for diagnosis and for monitoring efficacy of treatment of hsPDA.