N-terminal probrain natriuretic peptide (NT-proBNP) is elevated in patients with heart failure. Numerous clinical trials have evaluated the efficacy of spironolactone in heart failure; however, no studies have directly examined the effects of spironolactone treatment on NT-proBNP level. This study investigated whether NT-proBNP levels decrease with daily spironolactone treatment. The study consisted of 117 adult patients with heart failure. All participants were divided into 3 groups, class I, class II, and class III, according to the New York Heart Association classification system. Patients were randomly assigned to receive spironolactone or were treated with another drug, other than spironolactone, as placebo. NT-proBNP plasma samples were taken at baseline and after 6 mo of treatment. A total of 62 patients were treated with daily spironolactone; 55 patients were followed with available treatment without spironolactone. The baseline demographic and laboratory parameters were similar for patients in all groups. At the end of 6 mo, spironolactone-treated patients had significantly lower NT-proBNP levels and significantly better ejection fractions than did patients in all New York Heart Association classes who were not treated with spironolactone. Results suggest that spironolactone decreases plasma NT-proBNP concentrations, and that the measurement of plasma NT-proBNP levels may be helpful in assessing therapeutic efficacy in patients who are treated for heart failure.