Chronic heart failure (CHF) is a risk factor for sudden death. Temporal and spatial changes in repolarization are among the most studied mechanisms for inducing fatal ventricular arrhythmias. Beta blockers effectively reduce the risk of sudden death in CHF. Our aim in this study was to investigate changes induced by metoprolol and carvedilol on the QT variability index (QTVI), a new measure reflecting the temporal heterogeneity of cardiac repolarization. A total of 82 subjects, who were in New York Heart Association functional class II or III, underwent short-term spectral analysis of RR and QT variability before and after a 1-year course of high-dose metoprolol (40 subjects) or carvedilol (42 subjects) at baseline (rest) and after sympathetic stress (head-up tilt). At rest, both drug-treated groups had lower QTVI (p <0.001) than after placebo, but during tilt patients treated with carvedilol had a lower QTVI than those treated with metoprolol (p <0.05). Although both beta-blocker treatments helped to normalize the QTVI measured in normal subjects at rest, they each differentially altered the index after tilt. Carvedilol seemed to improve the QTVI more than metoprolol.