The aim of this study was to assess the variability in automated electrocardiogram (ECG) interpretation due to electrode positioning variations. Such variations were simulated by using a set of 746 body surface potential mappings from apparently healthy individuals and patients with myocardial infarction or left ventricular hypertrophy. Four types of electrode position changes were simulated, and the effect on ECG measurements and diagnostic classifications was determined by a computer program. At most 6% of the cases showed important changes in classification for longitudinal shifts. Transversal shifts causes less than 1.5% of important changes. An expert cardiologist, who analyzed a subset of 80 cases, agreed with the computer in 38 of 40 cases in which it made no change. In the 40 cases with large diagnostic changes, the cardiologist made no change in 18 cases. The effect of electrode position changes on ECG classification by an expert cardiologist was about half of the effect determined by computerized ECG classification. The effects on classification are significant; therefore, correct placement of chest electrodes remains mandatory.