In many patients, significant changes in ischemic mitral regurgitation (IMR) severity during exercise can be observed independent of the degree of IMR at rest. This study aimed to investigate the correlations between N-terminal fragment B-type natriuretic peptide (NT-proBNP) and echocardiography measurements at rest and at peak exercise in patients with moderate IMR who qualified for surgical revascularization. A total of 100 patients eligible for coronary artery bypass grafting, were included in this prospective study. All patients underwent exercise echocardiography. Additionally, the levels of NT-proBNP were measured at rest and after peak exercise. A positive correlation of absolute NT-proBNP levels with effective regurgitant orifice area (EROA) were observed and with tricuspid regurgitant peak gradient (TRPG) at peak exercise. Absolute ΔNT-proBNP during exercise and the tenting area at rest were independent predictors of severe IMR at peak exercise. The level of absolute ΔNT-proBNP during exercise and coaptation height at rest were the most important predictors of significant increases in TRPG. The best cutoff value for ΔNT-proBNP as a predictor for increases in EROA at peak exercise was 68.9 pg/mL and to predict an increase in TRPG ≥ 50 mmHg at peak exercise was 68 pg/mL. The level of ΔNT-proBNP during exercise was the most important parameter in predicting significant changes in IMR severity and pulmonary pressure. Based on the present data, it can be speculated that integration of the assessment of NT-proBNP at rest and at exercise might improve patient selection for valve surgery.