Simultaneous ischemia in two myocardial regions is a potentially lethal clinical condition often unrecognized whose corresponding electrocardiographic (ECG) patterns have not yet been characterized. Thus, this study aimed to determine the QRS complex and ST-segment changes induced by concurrent ischemia in different myocardial regions elicited by combined double occlusion of the three main coronary arteries. For this purpose, 12 swine were randomized to combination of 5-min single and double coronary artery occlusion: Group 1: left Circumflex (LCX) and right (RCA) coronary arteries (n = 4); Group 2: left anterior descending artery (LAD) and LCX (n = 4) and; Group 3: LAD and RCA (n = 4). QRS duration and ST-segment displacement were measured in 15-lead ECG. As compared with single occlusion, double LCX+RCA blockade induced significant QRS widening of about 40 ms in nearly all ECG leads and magnification of the ST-segment depression in leads V1-V3 (maximal 228% in lead V3, p < 0.05). In contrast, LAD+LCX or LAD+RCA did not induce significant QRS widening and markedly attenuated the ST-segment elevation in precordial leads (maximal attenuation of 60% in lead V3 in LAD+LCX and 86% in lead V5 in LAD+RCA, p < 0.05). ST-segment elevation in leads V7-V9 was a specific sign of single LCX occlusion. In conclusion, concurrent infero-lateral ischemia was associated with a marked summation effect of the ECG changes previously elicited by each single ischemic region. By contrast, a cancellation effect on ST-segment changes with no QRS widening was observed when the left anterior descending artery was involved.