OBJECTIVES: We sought to assess the variability of results obtained with thallium scintigraphy as a method for tracking the extent of myocardial ischemia in medically refractory patients with angina who are not suitable for coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. BACKGROUND: New therapies are being evaluated for patients with “no option” angina in whom medical therapy has failed. Nuclear techniques, like thallium scintigraphy, are used in multicenter trials to evaluate whether such therapies improve myocardial perfusion. However, the variability of test results is unknown in this patient group in a multicenter study. METHODS: The Angina Treatments: Lasers And Normal Therapies In Comparison (ATLANTIC) study was a randomized trial of transmyocardial laser revascularization (n = 182). Patients underwent dipyridamole thallium stress tests at baseline and 3, 6 and 12 months after enrollment. The control group (n = 90) was treated with constant medical therapy during the study and is a relevant group to investigate test variability. Test variability over time was quantified by the mean absolute change in the percentage of reversible perfusion defects between baseline and follow-up. RESULTS: Baseline percent myocardium with ischemia averaged 17.0 +/- 13.7% and did not change during follow- up. However, variations in the percent myocardium with reversible perfusion defects over time amounted to an average of 6 to 8 percentage points, or 43% to 55% of the baseline value. Only approximately 13% of this variability was attributable to variability in image reconstruction and analysis. CONCLUSIONS: As demonstrated in the ATLANTIC study, percent myocardial ischemia in control subjects receiving constant medical therapy varied in individual patients by an average of approximately 50%. This may limit the utility of thallium scintigraphy to detect improved myocardial perfusion over time in response to therapy.