Coronary artery disease (CAD) is the leading cause of morbidity and mortality in diabetics. Early diagnosis of CAD and identification of high-risk subgroups, followed by appropriate therapy, may therefore enhance survival. This study sought to determine the value of stress myocardial perfusion single-photon emission computed tomography (SPECT) with technetium-99m sestamibi to detect perfusion defects and predict cardiac events in asymptomatic diabetics. One hundred eighty asymptomatic diabetics without known CAD who underwent 2-day stress technetium-99m sestamibi SPECT were followed up for 36 +/- 18 months. End points were defined as hard (myocardial infarction or cardiac death) or total events (myocardial infarction, cardiac death, or late revascularization). Logistic regression analysis evaluated clinical variables, type of stress, exercise treadmill test (ETT), and SPECT as predictors of end points. Perfusion defects were found in 26% of patients (15% reversible, 6% mixed, and 5% fixed). Clinical or ETT variables were not associated with perfusion defect type or with hard events. However, male gender predicted total events (chi-square 3.3; p = 0.01). An abnormal SPECT significantly increased the risk of hard events (chi-square 5.4; p = 0.001) and total events (chi-square 7.4; p = 0.0001). Extensive defects determined the highest risk of total events (chi-square 18.8; p = 0.0001). Event rates increased according to SPECT: 2% of hard events per year and 5% of total events per year in patients with normal SPECT versus 9% per year and 38% per year, respectively, in those with abnormal SPECT. Importantly, a normal SPECT identified a relatively low-risk subgroup of patients. Thus, stress technetium-99m sestamibi SPECT was useful in evaluating asymptomatic diabetics for the presence of CAD, and effectively risk-stratified this population.