BACKGROUND: Previous studies have shown that myocardial perfusion single photon emission computed tomography (SPECT) provides incremental prognostic information in the general population, but the prognostic efficacy of nuclear testing in patients with diabetes mellitus is unclear. METHODS: We conducted a study with 1271 consecutively registered patients with diabetes and 5862 patients without diabetes with known or suspected coronary artery disease undergoing rest thallium 201/stress technetium 99m sestamibi dual-isotope myocardial perfusion SPECT with exercise or adenosine pharmacologic testing. Patients were followed up for at least 1 year. The successful follow-up rate was 92.4% for patients with diabetes and 94.0% for subjects without diabetes. The mean follow-up period was 23.7 +/- 7.7 months for the former group and 21.5 +/- 6.1 months for the latter. RESULTS: Over the follow-up period, patients with diabetes had significantly higher rates of hard events (cardiac death or nonfatal myocardial infarction) (4.3% per year versus 2.3% per year, P <.001) and higher total event rates (hard events and late revascularization) (9.0% per year versus 5.3% per year, P <. 001) compared with rates among patients without diabetes. Cox proportional hazards analysis revealed that nuclear testing added incremental value over clinical and historical variables among patients with diabetes (global chi(2) increased 46% for the exercise group [n = 619] and 88% for the adenosine group [n = 461]; both P <. 001). The event rates rose significantly as a function of summed stress score and summed difference score among both patients with diabetes and patients without diabetes (P <.001). The patients with diabetes with normal scans had relatively low hard event rates (1% to 2% per year), those with mildly abnormal scans had intermediate hard event rates (3% to 4% per year), and those with moderately to severely abnormal scans had relatively high hard event rates (>7% per year). CONCLUSIONS: The results of this study indicated that exercise and adenosine stress myocardial perfusion SPECT are valuable for risk stratification and management of patients with diabetes.