The objective of the present study was to examine the effect of induced ischemia on the morphology of the high frequency MD-QRS (HF-QRS) potentials in patients referred to Thallium stress myocardial perfusion (SPECT) imaging. High-resolution ECG waveforms from 12 leads were analyzed before, during, and following stress testing using BSP Biological Signal Processing Ltd. (Tel Aviv, Israel) system. The changes in the HF-QRS total energy were examined. Also conventional ST-T analysis for ischemic heart disease was performed. The results from the HF-QRS and the conventional ECG analysis were compared to the nuclear imaging results. The high frequency method detected 24 out of 28 of the ischemic patients (86%), and 37 out of 52 of the non-ischemic patients (71%). The conventional ST segment and T wave analysis detected only 11 out of 28 of the ischemic patients (39%), and 34 out of 52 of the non-ischemic patients (65%). In conclusion, the present study shows that the HF ECG has better clinical diagnostic performance compared to the conventional ECG based methods.