Objectives: To examine the effects of psychological stress on QT dispersion (QTd) among CAD patients and whether these effects are mediated via the development of myocardial ischemia. Methods: Psychological stress was induced using a public speaking task. Twelve-lead electrocardiograms (ECG) were recorded at rest, during mental stress, and during recovery. QTd was calculated as the difference between the longest and the shortest QT interval in the 12-lead ECG. Rest-stress myocardial perfusion imaging was also performed to detect mental stress-induced myocardial ischemia. Results: Mental stress induced a significant increase in QTd compared to the resting condition (P < 0.001). This effect persisted beyond the first 10 minutes of recovery (P < 0.001). QTd was significantly associated with the development of mental stress ischemia with ischemic patients having significantly higher QTd during mental stress than nonischemic patients (P = 0.006). This finding remained significant after controlling for possible confounding factors (P = 0.01). Conclusion: An acute psychological stress induces a significant increase in QTd, which persists for more than 10 minutes after the cessation of the stressor. This effect seems to be, at least partially, mediated by the development of mental stress-induced myocardial ischemia. (PACE 2009; 32:1178-1183).