Most patients with ST depression during adenosine infusion have reversible perfusion defects by single-photon emission computed tomographic (SPECT) perfusion images. Occasionally ST depression is observed in the setting of normal perfusion images. The outcome of such patients is controversial. We identified 65 patients who underwent gated SPECT perfusion imaging with adenosine as the stress agent. These patients were selected based on the following criteria: none had previous myocardial infarction or coronary revascularization, all were in sinus rhythm, and none had left bundle branch block. The 65 patients had normal SPECT images but ischemic ST response (≥1 mm ST depression). There were 52 women and 13 men who were 66 ± 13 years of age. History of diabetes mellitus was present in 16 patients (25%) and hypertension in 48 patients (74%). At a mean follow-up of 24 months, there were no cardiac deaths or myocardial infarctions, and there were 6 coronary revascularization procedures (2 coronary artery bypass graftings and 4 coronary stentings of 1-vessel coronary disease). One patient died of cancer. In conclusion, patients with no previous myocardial infarction or coronary revascularization who have normal SPECT images have a benign outcome despite the presence of ST depression (0% for death or myocardial infarction and 4.6%/year for coronary revascularization). Balanced ischemia could not be a common cause for discordant perfusion and ST response. © 2006 Elsevier Inc. All rights reserved.