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N-terminal pro brain natriuretic peptide (NT-proBNP) is released in response to increased myocardial wall stress and is associated with adverse outcome in acute myocardial infarction. However, little is known about the relationship between longitudinal deformation indices and NT-proBNP.We prospectively included 611 patients with acute myocardial infarction admitted to a tertiary centre and performed echocardiography within 48 h of admission. Global longitudinal myocardial function was assessed by two-dimensional speckle tracking simultaneously with measurement of plasma NT-proBNP. A significant linear relationship between NT-proBNP and global longitudinal strain (GLS) was found (P < 0.0001, r = 0.62). Weaker correlation was found between NT-proBNP and left ventricular ejection fraction (LVEF; P < 0.0001, r = – 0.44). GLS emerged on multivariable analysis including age, sex, estimated glomerular filtration rate, Killip class ≥2, diabetes, hypertension, presence of ST segment elevation, anterior infarction, troponin level, left atrial volume index, mitral valve deceleration time, and E/e' as the strongest predictor of log(NT-proBNP) (P < 0.0001). In patients with preserved systolic function (LVEF >45%), GLS remained strongly correlated with NT-proBNP (P < 0.0001, r = 0.50). The C-statistic associated with prediction of upper vs. lower quartiles of NT-proBNP was significantly higher for GLS compared with LVEF (0.76 vs. 0.56; P < 0.0001).Left ventricular longitudinal function assessed by GLS exhibits a stronger association with NT-proBNP levels in acute myocardial infarction compared with LVEF. In patients with apparently preserved systolic function, GLS is superior to LVEF in identifying increased neurohormonal activation.