Objective The aim of the study was to evaluate the value of the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) as an early diagnostic marker for chronic heart failure (CHF) in hypothyroid patients with ischemic heart disease (IHD). Materials and methods A total of 120 patients with an age range between 42 and 64 years participated in the study. All patients were classified into four groups: the master first group includes 30 patients with IHD, CHF functional class II–III and hyperthyroidism; the second group includes 30 patients with IHD and CHF functional class II–III, but with normal thyroid function; the third group includes 30 hyperthyroid patients without CHF or IHD; and the fourth group includes 30 hyperthyroid patients with IHD, without CHF. All patientswere subjected to the following: full clinical and functional assessment, measurement of NT-proBNP, echocardiography, and the 6-min walk test. Results NT-proBNP levels were high in all studied groups. NT-proBNP levels showed no significant difference between patients of second and fourth group. The master first group had the highest significant NT-proBNP concentrations than other studied groups. Thyroid hyperfunction in patients with IHD appears to stimulate the natriuretic peptides secretion at a level exceeding what is recommended for the initial diagnosis of CHF. Conclusion The highest NT-proBNP level in hyperthyroid patients with IHD apparently is caused by stimulation of natriuretic peptide secretion by both thyroid hyperfunction and myocardial ischemic changes, which determine the need to check out the cut-off value of NT-proBNP level as a serological marker for the initial diagnosis of heart failure of such patients’ category.