Elevated levels of N-terminal pro brain natriuretic peptide (NT-proBNP) are associated with adverse cardiovascular outcome after ST elevation myocardial infarction (STEMI). We hypothesized that decreasing acuteness-score (based on the electrocardiographic score by Anderson-Wilkins acuteness score of myocardial ischemia) is associated with increasing NT-proBNP levels and the impact of decreasing acuteness-score on NT-proBNP levels is substantial in STEMI patients with severe ischemia.In 186 STEMI patients treated with primary percutaneous coronary intervention (pPCI), the severity of ischemia (according to Sclarovsky-Birnbaum severity grades of ischemia) and the acuteness-score were obtained from prehospital ECG. Patients were classified according to the presence of severe ischemia or non-severe ischemia and acute ischemia or non-acute ischemia. Plasma NT-proBNP (pmol/L) was obtained after pPCI within 24hours of admission and was correlated with the acuteness-score.NT-proBNP levels were median (25th-75th interquartile) 112 (51-219) pmol/L in patients with non-severe ischemia (71.5%) and 145 (79-339) in patients with severe ischemia (28.5%) (p=0.074). NT-proBNP levels were highest in patients with severe and non-acute ischemia compared to those with severe and acute ischemia (182 (98-339) pmol/L vs 105 (28-324) pmol/L, p=0.012). There was a negative correlation between acuteness-score and log(NT-proBNP) in patients with severe ischemia (r=0.395, p=0.003), which remained significant in multilinear regression analysis (β=-0.155, p=0.007). No correlation was observed between the acuteness-score and log(NT-proBNP) in patients with non-severe ischemia (p=0.529) or in the entire population (p=0.187).In STEMI patients with severe ischemia, neurohormonal activation is inversely associated with ECG patterns of acute myocardial ischemia.