Background: This study compared the prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging with that of treadmill exercise score in medically treated patients with coronary artery disease (CAD) Methods and Results: The treadmill exercise score was derived from exercise duration, degree of ST segment depression, and the treadmill anginal index. There were 121 patients with no CAD and 316 patients with angiographically defined CAD (>-50% diameter stenosis of one or more vessels). During a mean follow-up of 29 months, there were 35 cardiac deaths or nonfatal myocardial infarctions. Multivariate Cox survival analysis showed the extent of thallium imaging abnormality and CAD to be independent predictors of prognosis. On the other hand, the treadmill exercise score was not a significant predictor even on univariate analysis. The results of thallium uptake were the strongest independent predictors of prognosis and in addition provided incremental prognostic power to coronary angiography (X2=29 for SPECT, 27 for coronary angiography, and 37 for both). Conclusions: Thus exercise SPECT thallium imaging is significantly better than the treadmill exercise score in risk assessment. The size of the perfusion abnormality is an important predicator of prognosis. © 1994 American Society of Nuclear Cardiology.