Inotropic stress using graded dobutamine infusion has evolved as an alternative form of pharmacologic stress in conjunction with perfusion and functional imaging for evaluation of coronary heart disease. However, the prognostic value of technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging in patients undergoing dobutamine stress testing for the detection of coronary artery disease is unclear. Accordingly, 61 patients undergoing coronary arteriography for the evaluation of chest pain on the basis of symptoms and treadmill exercise electrocardiography underwent SPECT imaging at rest and during stress. Patients were followed up for 19 +/- 11 months (2 to 33) during which 2 died, 2 had acute myocardial infarction, 13 developed unstable angina, and 3 had congestive heart failure. Univariate Cox regression analysis revealed that those with reversible defects (95%) and defects in multiple vascular territories (80%) on SPECT had a greater number of cardiac events compared to those without (59% [p = 0.02] and 34% [p = 0.002], respectively). The number of reversible (3.9 +/- 2.1) and fixed (2.3 +/- 2.0) segments (12-segment model) were greater in patients with cardiac events compared to those without, (2.3 +/- 2.5, p = 0.009 and 1.1 +/- 2.0, p = 0.02) respectively. When multivariate analysis was performed using clinical, exercise testing, and SPECT variables, the independent predictors of cardiac events were a history of myocardial infarction (p <0.001), number of reversible segments (p = 0.001), and presence of defects in multiple vascular territories (p = 0.01). In summary, dobutamine stress Tc-99m sestamibi SPECT is a powerful predictor of future cardiac events in patients undergoing coronary arteriography for evaluation of chest pain and may be used to stratify patients for further intervention.