Rotation of the heart in relation to surface electrocardiographic (ECG) electrodes when a patient turns to one side has been reported to cause ST-segment shifts, triggering false alarms with continuous ST-segment monitoring. We prospectively analyzed ST-segment and QRS complex changes in both standard and derived ECGs in 40 subjects (18 with heart disease and 22 healthy) in supine, right- and left-lying positions. Of the 40 subjects, 6 (4 cardiac, 2 healthy) developed positional ST deviations of 1 mm or more on the standard ECG. In the derived method, five of the same six subjects showed ST-segment deviation of which most occurred in the left-lying position. Positional ST changes were most frequent for males and for cardiac patients (33%). Changes in QRS complex morphology were common on the standard (28 of 40, 70%) and less frequent on the derived ECGs (17 of 40, 43%), occurring in both healthy and cardiac subjects. QRS axis changes occurred only on the standard ECG. It was concluded that (1) right and left side-lying positions frequently induce clinically significant ECG changes; (2) positional ST-segment deviation is less frequent than previously reported and is most likely to occur in males with cardiac disease; and (3) the derived method is less prone to positional QRS changes than the standard ECG.