The prognostic value of myocardial perfusion imaging in African-Americans is unknown. This study compared the prediction of cardiac events of stress technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging in symptomatic Caucasian and African-American patients. Prospectively collected stress Tc-99m sestamibi tomographic imaging data from 4 medical centers, with follow-up information in 1,086 Caucasian and African-American patients, were analyzed in a core statistical laboratory. Primary events of cardiac death and nonfatal myocardial infarction and secondary events of all-cause mortality were analyzed using Kaplan-Meier survival analysis and Cox proportional-hazards multivariable model. Normal images in both African-Americans and Caucasians were associated with a low-annual cardiac event rate, whereas abnormal images were significantly associated with a higher cardiac event rate. The highest predictor of cardiac events was multivessel abnormality in both races. Use of this technique could identify patients at high risk and potentially reduce the high-cardiac event rate in African-Americans by utilizing appropriate therapies.