This study aimed to determine whether increased QT interval variability is associated with an increased risk for ventricular tachycardia(VT) or ventricular fibrillation(VF), documented by interrogation of the implantable cardioverter-defibrillator (ICD), in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. Unstable repolarization has been proposed as a risk factor for re-entrant arrhythmias, but confirmatory data from clinical trials are lacking. The QT variability was assessed in 10-min, resting high-resolution electrocardiogram recordings at study entry using a semiautomated algorithm that measured beat-to-beat QT duration in 817 MADIT II patients. The incidence of VT/VF requiring device therapy was determined by ICD interrogation. Median normalized QT variability(QTVN) was 0.179 and 0.125, respectively, in patients with VT/VF versus those without VT/VF(p=0.001); QTVI(QTVN adjusted for heart rate variance) also was significantly(p < 0.05) higher in VT/VF patients than in those without VT/VF. Either QTVN or QTVI was linked with a significantly higher probability of VT/VF: two-year risk of VT/VF from Kaplan-Meier curves was 40%in highest quartile versus 21%in lower quartiles for QTVN, and 37%versus 22%for QTVI (p< 0.05 for each). In multivariate Cox regression models adjusting for clinical covariates(race, New York Heart Association functional class, time after myocardial infarction), top-quartile QTVI and QTVN were independently associated with VT/VF(hazard ratio for QTVN 2.18, 95%confidence interval1.34 to 3.55, p=0.002; hazard ratio for QTVI 1.80, 95%CI 1.09 to 2.95, p=0.021). In postinfarction patients with severe left ventricular dysfunction, increased QT variability, a marker of repolarization lability, is associated with an increased risk for VT/VF. This study aimed to determine whether increased QT interval variability is associated with an increased risk for ventricular tachycardia (VT) or ventricular fibrillation (VF), documented by interrogation of the implantable cardioverter-defibrillator (ICD), in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. Unstable repolarization has been proposed as a risk factor for re-entrant arrhythmias, but confirmatory data from clinical trials are lacking. The QT variability was assessed in 10-min, resting high-resolution electrocardiogram recordings at study entry using a semiautomated algorithm that measured beat-to-beat QT duration in 817 MADIT II patients. The incidence of VT / VF requiring device therapy was determined by ICD interrogation. Median normalized QT variability (QTVN) was 0.179 and 0.125, respectively, in patients with VT / VF versus those without VT / VF (p = 0.001); QTVI (QTVN adjusted for heart rate variance) her in VT / VF patients than in those without VT / VF. Either QTVN or QTVI was linked with a significantly higher probability of VT / VF: two-year risk of VT / VF from Kaplan-Meier curves was 40% in highest quartile versus 21% in lower quartiles for QTVN, and 37% versus 22% for QTVI (p <0.05 for each). In multivariate Cox regression models adjusting for clinical covariates (race, New York Heart Association functional class, time after myocardial infarction), top -quartile QTVI and QTVN were independently associated with VT / VF (hazard ratio for QTVN 2.18, 95% confidence interval 1.34 to 3.55, p = 0.002; hazard ratio for QTVI 1.80, 95% CI 1.09 to 2.95, p = 0.021). In postinfarction patients with severe left ventricular dysfunction, increased QT variability, a marker of repolarization lability, is associated with an increased risk for VT / VF.