There is overlap in myocardial viability detection by thallium-201 uptake and contractile reserve (CR) using low-dose dobutamine (LDD). The dual isotope protocol was modified in this study by acquiring thallium-201 images using LDD to enhance viability detection in addition to coronary flow reserve assessment. One hundred twenty-four patients with coronary disease underwent gated single-photon emission computed tomographic thallium-201 imaging at rest with LDD (10 microg/kg/min) during acquisition followed by stress technetium-99m sestamibi myocardial perfusion (MP) imaging with dobutamine, adenosine, or treadmill exercise. F-18-fluorodeoxyglucose (FDG) positron emission tomography was obtained in 41 patients. Myocardial perfusion (MP) imaging was divided into normal, fixed, and ischemic segments, and subclassified by wall motion and/or thickening changes between 1-hour poststress and LDD into normal, fixed, or improved dysfunctional segments (CR present). Mean left ventricular ejection fraction was 39% at 1 hour after stress and 47% with LDD (p <0.001). In dysfunctional myocardium, CR was significantly higher (p <0.001) in ischemic (233 of 368) and fixed segments (150 of 335) than in normal MP segments (43 of 220). Combined MP and CR analysis showed higher accuracy and negative predictive value in identifying FDG-viable myocardium than either method alone, whereas a high positive predictive value was maintained, similar to both markers. Quantitative analysis showed significant increased wall motion and thickening with LDD compared with 1 hour after stress, which was highest in ischemic segments and lowest in fixed segments. Thus, LDD dual isotope is a practical protocol that improves viability detection by simultaneous MP and CR analysis in addition to coronary flow reserve assessment in 1 study. Moreover, it requires no extra imaging time or radioactivity than the routine protocol.