Background. The ability of the size of a total myocardial perfusion defect (MPD) to detect extensive coronary artery disease (CAD) is currently suboptimal with exercise thallium 201 single photon emission computed tomography (SPECT). To improve its performance, exercise electrocardiography and indirect scintigraphic markers of extensive CAD were proposed (increased right ventricular Tl-201 uptake, lung-to-heart [L/H] ratio, and left ventricular transient ischemic dilation ratio). We aimed to determine the additive value of these criteria for the detection of extensive CAD. Methods and Results. The population included 338 patients who underwent exercise Tl-201 SPECT and coronary angiography. Patients were classified as having extensive CAD (left main, multivessel, or 1-vessel proximal left anterior descending CAD) or limited CAD (1-vessel disease other than proximal left anterior descending CAD or no CAD). First, Tl-201 SPECT provided higher diagnostic value than exercise electrocardiography. Second, age, percent target heart rate achieved, total MPD, and L/H ratio were independent predictors of extensive CAD. Third, visually estimated abnormal right ventricular Tl-201 uptake did not present additional information. Fourth, L/H ratio presented a higher diagnostic accuracy than left ventricular transient ischemic dilation ratio. Conclusions. With exercise Tl-201 SPECT, age, percent target heart rate achieved, total MPD, and L/H ratio were independent predictors of extensive CAD. (J Nucl Cardiol 2002;9:161-8.)