OBJECTIVE This study was designed to evaluate the differential prognostic value of gated single-photon emission computed tomographic imaging (SPECT) imaging in an ethnically diverse multicenter registry. BACKGROUND Ethnic minority patient populations have reportedly higher coronary heart disease mortality with greater comorbidity and a clustering of risk factors at a significantly younger age when compared with Caucasian, non-Hispanic patients. Despite our increasingly diverse population, the predictive accuracy of cardiac imaging in ethnic minority patients is ill-defined. METHODS A total of 7,849 patients were prospectively enrolled in a registry of patients undergoing exercise (44%) or pharmacologic stress (56%) technetium-99m tetrofosmin SPECT. Scans were scored using a 20-segment myocardial model with a 5-point severity index. Multivariable Cox proportional hazards models were employed to assess time to death or myocardial infarction. RESULTS A total of 1,993 African-American, 464 Hispanic, and 5,258 Caucasian non-Hispanic patients underwent SPECT imaging. African-American and Hispanic patients more often had a history of stroke, peripheral arterial disease, angina, heart failure, diabetes, hypertension, and smoking at a younger age. Moderate or severely abnormal SPECT scans were noted in 21%, 17%, and 13% of African-American, Hispanic, and Caucasian non-Hispanic patients, respectively (p < 0.0001). Cardiovascular death rates were highest for ethnic minority patients (p < 0.0001). Annual rates of ischemic heart disease death ranged from 0.2% to 3.0% for Caucasian non-Hispanic and 0.8% to 6.5% for African-American patients with low-risk to severely abnormal SPECT scans (p < 0.0001). For post-stress ejection fraction <45%, annualized risk-adjusted death rates were 2.7% for Caucasian non-Hispanic patients versus 8.0% and 14.0% for African-American and Hispanic patients (p < 0.0001). CONCLUSIONS The current results from a large observational registry reveal that exercise and pharmacologic stress SPECT effectively predicts major cardiovascular events in a large cohort of African-American and Hispanic patients evaluated for suspected myocardial ischemia. These results provide further evidence that ethnic minority patient populations have a worsening outcome related to cardiovascular disease.