The purpose of this study was to investigate the effects of T-wave amplitude and ECG lead on beat-to-beat QT interval variability (QTV) in patients with myocardial infarction (MI) compared to healthy subjects. Standard resting 12-lead ECGs of 79 MI patients and 69 healthy subjects were investigated. Beat-to-beat QT intervals were measured separately for each lead using a template matching algorithm. In addition, we extracted the beat-to-beat T-wave amplitude in each lead. We computed the standard deviation of beat-to-beat QT intervals as a marker of QTV for both healthy subjects and MI patients. Significant QTV differences were observed between the 12 ECG leads as well as between the groups of healthy subjects and MI patients. Beat-to-beat QTV was significantly higher in MI patients than in healthy subjects for half of the leads. Furthermore, significant T-wave amplitude differences across leads and between groups were observed. A significant inverse relation between beat-to-beat QTV and T-wave amplitude was demonstrated. The group differences in QTV remained significant after co-varying for the T-wave amplitude. In conclusion, the increase in beat-to-beat QTV that has been repeatedly reported in patients with MI is partly due to the lower T-wave amplitudes. However, QTV remains significantly increased in MI patients after covarying for this effect.