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The prognostic significance of ischemic electrocardiographic (ECG) changes during Regadenoson vasodilator stress in patients with normal single-photon emission computed tomographic myocardial perfusion imaging (SPECT-MPI) is not well described. Of 2473 patients who underwent Regadenoson vasodilator stress testing, 43 (77% women, mean age 72 ± 10 years) patients were included in the study. During a mean follow-up of 14 ± 7 months, cardiac death occurred in 1 patient; 5 patients underwent coronary revascularization and none had myocardial infarction. The annual rate of cardiac death and coronary revascularization was 1.9% and 9.9%, respectively. The finding of ischemic ECG changes with normal SPECT-MPI during regadenoson vasodilator stress testing is uncommon, occurs primarily in older women, and is associated with moderately higher subsequent cardiac event rate.