In cardiac resynchronization therapy (CRT), the morphology of the QRS complex plays an important role in the determination of the pacing site and effectiveness of stimulation. Review of the electrocardiograms (ECGs) of 737 patients with a CRT device showed a negative QRS complex in lead I during right ventricular (RV) pacing and a positive QRS complex during left ventricular (LV) pacing in four patients. The RV lead was positioned in the high RV septum and the coronary sinus leads in a posterior or postero-lateral basal level. Reversed ECG lead or pacemaker lead connection, anodal RV stimulation, and scar tissue-related depolarization abnormalities were excluded as possible causes. Pacing from the high RV septum may rarely lead to a negative QRS complex and basal positions of the LV lead to a positive QRS complex in lead I during LV pacing. The lead I paradox becomes obvious when both phenomena, that are not interrelated, are present in the same patient.