Background: The aim of the Endocardial T-Wave Alternans Study was to prospectively assess thepresence of T-wave alternans (TWA) or beat-to-beat repolarization changes on implantable cardioverter-defibrillator (ICD)-stored electrograms (EGMs) immediately preceding the onset of spontaneous ventriculartachycardia (VT) or fibrillation (VF). Methods: Thirty-seven VT/VF episodes were compared to 116 baseline reference EGMs from the same57 patients. A Bayesian model was used to estimate the T-wave waveform in each cardiac beat and a setof 10 parameters was selected to segment each detected T wave. Beat-by-beat differences in each T-waveparameter were computed using the absolute value of the difference between each beat and the followingone. Fisher criterion was used for determining the most discriminant T-wave parameters, then top-Mranked parameters yielding a normalized cumulative Fisher score>95% were selected, and analysis wasapplied on these selected parameters. Simulated TWA EGMs were used to validate the algorithm. Results: In the simulation study, TWA was detectable even in the case of the smallest simulatedalternans of 25μV. In 13 of the 37 episodes (35%) occurring in nine of 16 patients, significant largerbeat-to-beat variations before arrhythmia onset were detected compared to their respective references(median one positive episode per patient). Parameters including the T-wave apex amplitude seem themore discriminant parameters.Conclusions:Detection of beat-by-beat repolarization variations in ICD-stored EGMs is feasible ina significant subset of cases and may be used for predicting the onset of ventricular arrhythmias.