To evaluate the sensitivity of electrocardiogram (ECG) versus single photon emission computed tomography (SPECT) assessments of ischemia in patients with anxiety disorders (AD) and the extent to which patients exhibit poorer exercise performance, compared with patients without AD. Patients referred for nuclear exercise stress testing (N = 2271) underwent a structured psychiatric interview (PRIME-MD) to assess for AD. Exercise performance parameters were assessed during ECG treadmill testing, after which patients underwent SPECT imaging. Analyses revealed that patients with AD exhibited lower peak exercise systolic blood pressure and rate pressure product than patients without AD. When major depressive disorder was included as an additional covariate, the previous results became trends. Results also indicated a lower rate of electrically positive ecg tests and a higher rate of false-negative diagnoses of myocardial ischemia according to ecg among patients with AD. Including major depressive disorder as a covariate rendered the effects of ad nonsignificant. There was no evidence of reduced exercise performance in patients with AD. Findings suggest that AD may be associated with mild impairments in cardiovascular exercise reactivity and may also alter the detection of myocardial ischemia using ecg assessments in patients referred for exercise stress testing. However, the influence of AD appears to be moderated by comorbid depression. Results suggest that exercise test performance and detection of ischemia may be influenced by mood and/or anxiety disorders and that greater efforts should be made to include routine mood and/or anxiety disorder screening as part of exercise stress testing protocols.