Background To evaluate the relevance of stress-induced decrease in left ventricular ejection fraction (LVEF) in patients with type-2 diabetes. Methods A total of 684 diabetic patients with available rest and post-stress gated myocardial perfusion single-photon emission computed tomography (MPS) data were enrolled. An automated algorithm was used to determine the perfusion scores using a 17-segment model. LVEF drop was considered significant if the post-stress LVEF was ≥5% below the rest value. Follow-up data were available in 587 patients that were followed for the occurrence of cardiac death, nonfatal myocardial infarction, or unstable angina requiring revascularization. Results A post-stress LVEF drop ≥5% was observed in 167 (24%) patients. Patients with LVEF drop had higher summed stress score (p 2 7.7, p Conclusions In diabetic patients stress-induced ischemia is an independent predictor of post-stress LVEF drop; however, a reduction in LVEF is detectable also in patients with normal perfusion. Finally, post-stress LVEF drop increases the risk of subsequent cardiac events in diabetic patients.