Background Exercise thallium-201 imaging provides a noninvasive estimate of the amount of myocardium presumed to be at risk of infarcting should a complete occlusion of the coronary stenosis occur. The relationship between the size of the exercise thallium perfusion defect and the extent of myocardium supplied by a diseased coronary artery has not been established. This study evaluates that presumed correlation. Methods Patients were injected intravenously with technetium-99m sestamibi during acute myocardial infarction before thrombolysis or conventional therapy to quantify the myocardium at risk. Twenty-six patients who underwent risk-area assessment subsequently underwent clinically driven, predischarge, submaximal exercise imaging with thallium-201. The exercise testing was performed on day 7 ± 2 days. A conventional polar map display was used to quantify the perfusion defect. Results The myocardium at risk determined by technetium-99m sestamibi at the time of infarction was 30% ± 20% of the left ventricle. The mean exercise thallium-201 defect was 34% ± 22% of the left ventricle. The exercise defect tended to be slightly larger than the myocardium at risk (4% ± 10% of the left ventricle, P =.05). There was a close correlation between the 2 measurements (r = 0.89, SE = 9.4, P <.0001). Conclusions This study shows a close correlation between the myocardium “at risk” assessed acutely by technetium-99m sestamibi and the “presumed at-risk area” determined by thallium-201 imaging on predischarge exercise testing. This finding supports the concept that the size of the exercise thallium defect caused by coronary stenosis indicates the likely size of a myocardial infarction resulting from occlusion of that stenosis. (Am Heart J 2003;145:357-63.)