The prevalence of silent myocardial ischemia (SMI) seems to be above average in diabetic subjects. As routine screening is costly, identifying high-risk populations is mandatory. This study aimed to estimate the prevalence of SMI in diabetic subjects and in controls and to define the diabetic population at risk. We studied 353 asymptomatic caucasian subjects (217 with diabetes and 136 controls matched by age, sex, and cardiovascular risk factors) with normal resting ECG. The diabetic group included 39 type 1 and 178 type 2 diabetics (age 57±11 yr, 162 males/55 females). Subjects performed the Treadmill Test (TT) and, when abnormal, underwent single-photon emission computed tomography (SPECT) with exercise testing or dipyridamole injection. Coronary angiography was performed if the SPECT was suggestive of ischemia. TT was positive in 16 (8.5%) diabetics: 3 with type 1 and 13 with type 2. No controls had positive TT. SPECT was performed in 13 subjects and was positive in 10; angiography was performed in 7 and identified significant lesions in all cases. Patients with SMI were older and had a higher prevalence of autonomic neuropathy, hypertension, and dyslipidemia than those without. Microalbuminuria was also higher in the SMI group (613±211 vs 72±245 mg/d; p<0.05). We conclude that diabetic patients aged over 60 with autonomic neuropathy and other cardiovascular risk factors should be screened for the presence of SMI especially if they have increased microalbuminuria.