AIMS: The Cardiac Resynchronization-Heart Failure (CARE-HF) study demonstrated that cardiac resynchronization therapy (CRT) could reduce morbidity and mortality and improve cardiac function in patients with moderate or severe heart failure secondary to left ventricular systolic dysfunction and markers of cardiac dyssynchrony. The purpose of this analysis was to investigate the effect of CRT on plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a powerful marker of cardiac dysfunction and prognosis. METHODS AND RESULTS: Blood samples were collected routinely at baseline and 3 and 18 months. Plasma was separated by cool centrifugation and stored at -70 degrees C until transported to a central laboratory for analysis of NT-pro-BNP using a standard commercial assay. Cardiac function was assessed echocardiographically. At baseline, median plasma concentration of NT-pro-BNP was similar in patients assigned to CRT or medical therapy [1920 pg/mL (inter-quartile range (IQR) 744-4288) and 1809 pg/mL (IQR 719-3949), respectively]. The differences in medians between the CRT and medical therapy groups were highly significant at both 3 months (537 pg/mL; P < 0.0001) and 18 months of follow-up (567 pg/mL; P < 0.0001). These differences could not be accounted for by changes in pharmacological therapy or renal function but were associated with improvement in ventricular volumes and function. CONCLUSION: CRT exerts an early and sustained reduction in NT-pro-BNP. This appears to reflect improvements in ventricular function. NT-pro-BNP may be a simple method for monitoring the effects of CRT.