BACKGROUND Technetium 99m-labeled sestamibi and tetrofosmin tomography have shown high diagnostic accuracy in the detection of coronary artery disease (CAD). However, few data are available comparing sestamibi and tetrofosmin imaging in the same patients. The aim of the study was to determine the image quality of the two tracers and to compare the results of exercise sestamibi and tetrofosmin tomography in the same patients. METHODS The results of exercise-rest sestamibi and tetrofosmin myocardial tomography were compared in 32 patients with suspected or known CAD who underwent coronary angiography. Image quality was evaluated subjectively. Regional tracer distribution was visually assessed and quantitatively measured in 22 segments/patient. RESULTS At coronary angiography, 7 patients had normal coronary vessels, 11 single-vessel, and 14 multivessel CAD (> or =50% luminal stenosis). Image quality judged visually was comparable with the two tracers. Heart/lung and heart/liver ratios for sestamibi and tetrofosmin were not different. At visual analysis, 68% of the patients with CAD had abnormal findings with sestamibi and 76% with tetrofosmin (p = NS). At quantitative analysis, 92% of the patients with CAD had abnormal findings with sestamibi and 96% with tetrofosmin (p = NS). At both visual and quantitative analyses, sensitivity, specificity, and diagnostic accuracy in the detection of individual stenosed vessels were not different between the two tracers. Moreover, for both tracers sensitivity, specificity, and diagnostic accuracy in the detection of diseased vessels were significantly higher (all p < 0.05) at quantitative compared with visual analysis. Finally, defect size and severity were similar for the two tracers. CONCLUSIONS Exercise-rest sestamibi and tetrofosmin tomography yielded images of comparable quality and provided similar results in the identification of patients with CAD and in the detection of the individual stenosed coronary vessels.