Background: Increased QT Variability (QTVI) is predictive of life threatening arrhythmias in vulnerable patients. The predictive value of QTVI is based on resting ECGs, and little is known about the effect of acute exercise on QTVI. The relation between QTVI and arrhythmic vulnerability markers such as T-wave alternans (TWA) has also not been studied. This study examined the effects of exercise on QTVI and TWA in patients with arrhythmic vulnerability., Methods: Digitized ECGs were obtained from 47 ICD patients (43 males; age 60.9 +/- 10.1) and 23 healthy controls (18 males; age 59.7 +/- 9.5) during rest and bicycle exercise. QTVI was assessed using a previously validated algorithm and TWA was measured as both a continuous and a categorical variable based on a priori diagnostic criteria., Results: QTVI increased with exercise in ICD patients (-0.79 +/- 0.11 to 0.36 +/- 0.08, P < 0.001) and controls (-1.50 +/- 0.07 to -0.19 +/- 0.12, P < 0.001), and QTVI levels were consistently higher in ICD patients than controls during rest and exercise (P < 0.001). The magnitude of QTVI increase from baseline levels was not larger among ICD patients versus controls (P > 0.20). Among ICD patients, elevated exercise QTVI was related to lower LV ejection fraction and inducibility of ischemia (P < 0.05). QTVI at rest correlated with exercise TWA (r = 0.54, P = 0.0004)., Conclusions: QT variability increases significantly with exercise, and exercise QTVI is related to other well-documented markers of arrhythmic vulnerability, including low ejection fraction, inducible ischemia, and TWA. Resting QTVI may be useful in the risk stratification of individuals incapable of performing standard exercise protocols.