Objective To investigate the association between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and the incidence of new-onset atrial fibrillation (AF) in patients with ischemic heart failure. Methods This study involved 120 patients with ischemic heart failure, characterized by sinus rhythm and a reduced ejection fraction (EF < 40%). NT-proBNP levels were measured at baseline, 6 months, and 12 months. At the 12-month follow-up, patients underwent 12-lead electrocardiography (EKG) or Holter monitoring to identify new-onset AF. Patients were classified into an AF group (n=44) and a non-AF group (n=76). Clinical characteristics and echocardiographic data were reviewed. Receiver operating characteristic (ROC) curves were employed to ascertain the optimal NT-proBNP threshold for predicting new-onset AF, and logistic regression analysis was used to evaluate the prognostic impact of NT-proBNP levels. Results New-onset AF was detected in 36.7% of the cohort. Significant elevations in functional capacity (NYHA class), NT-proBNP levels, E/A ratio, E/E' ratio, pulmonary artery systolic pressure (PASP), pulmonary capillary wedge pressure (PCWP), left atrial volume (LAV), and left atrial volume index (LAVI) were observed in the AF group compared to the non-AF group (P<0.05). NT-proBNP levels demonstrated positive correlations with these echocardiographic parameters (P<0.05). ROC curve analysis identified a baseline NT-proBNP cutoff value of 2357 pg/mL as the most predictive of new-onset AF, with 69% sensitivity and 83% specificity (AUC = 0.825, 95% CI: 0.722-0.924, P<0.001). Logistic regression analysis further established NT-proBNP as the only independent predictive predictor of new-onset AF (OR = 1.24, 95% CI: 1.08-1.43, P=0.001). Conclusions Serum NT-proBNP level is of certain value in prediction of the new-onset AF in patients with ischemic heart failure.