The objective is to examine the correlation between plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) echocardiographic parameters in the first 28 days of life in very-low-birth-weight infants (VLBWI). VLBWI admitted to the Neonatal Intensive Care Unit (NICU) at Hospital Puerta del Mar, Spain, from January 2015 to January 2017 were prospectively enrolled. Weekly determination of plasma NT-proBNP (pg/mL), and echocardiograms were done during the first 28 days of life. 101 preterm infants with a mean GA of 28.85 weeks (± 1.85 SD) and mean birth weight of 1152 g (± 247.4 SD) were included. A total of 483 echocardiograms and 139 NT-proBNP determinations were performed. We found a negative correlation between plasma NT-proBNP levels and diastolic velocities: mitral A′ (ρ = − 0.15, p = 0.04), mitral E′ (ρ = − 0.17, p = 0.02), tricuspid A′ (ρ = − 0.20, p = 0.006), tricuspid E′ (ρ = − 0.24, p = 0.0009). In the first 24 h of life, NT-proBNP levels were strongly correlated with mitral A′ and E′ velocities in patients with no patent ductus arteriosus (PDA) (ρ = − 0.75, p = 0.04). In preterm patients, elevated NT-proBNP levels are related to worse diastolic myocardial function. In the first 24 h, this correlation is much stronger in the absence of PDA.