Background: Intravenous adenosine in conjunction with myocardial perfusion imaging is commonly used for the detection of coronary artery disease and risk assessment. We have previously shown that patients with ischemic changes on the 12-lead electrocardiogram (ECG) in response to adenosine but with normal perfusion pattern have a benign outcome on short-intermediate follow-up. The long-term outcome of these patients is unknown. Methods: Patients with ischemic ECG response (≥ 1 mm ST depression) to adenosine infusion but with normal perfusion on single-photon emission computed tomography (SPECT) imaging in the absence of a history of myocardial infarction or coronary revascularization were followed up for mortality, myocardial infarctions, and coronary revascularization. Results: The cohort consisted of 73 patients (81% women) who were followed up for mortality for a mean of 61 ± 15 months. There were 10 deaths, and the cause of death was determined to be non-cardiac in half of those. Follow-up for the other endpoints was complete for 21 ± 10 months during which no patient had myocardial infarction and seven underwent coronary revascularization. Conclusions: Patients with ischemic ECG response to intravenous adenosine administration and normal perfusion on SPECT are at low risk of cardiovascular events. The ST segment response to adenosine in this setting is likely related to non-ischemic mechanisms. Copyright © 2009 Via Medica.