BACKGROUND The aim of this study was to assess the accuracy of stress 99m technetium tetrofosmin myocardial perfusion imaging for the diagnosis of in stent stenosis (ISS). METHODS We studied 72 patients who underwent exercise or dobutamine stress 99m technetium tetrofosmin imaging, 0.9+/-0.5 years after percutaneous coronary interventions in which stents were deployed. Coronary angiography was performed within 3 months of the stress test. ISS was defined as > or =50% stenosis in a coronary segment with previous stenting. Significant coronary artery disease (CAD) was defined as > or =50% stenosis within or outside the stented coronary segment. RESULTS The stent was deployed in 1 coronary artery in 52 patients, and in 2 coronary arteries in 20 patients (a total of 92 detected in 42 (58%) patients (51 stents). Reversible perfusion abnormalities were present in 34 of patients with ISS (sensitivity=81%, CI 70-94). Regional sensitivity for diagnosis of stenosis per stent was 76% (CI 65-88), specificity was 83% (CI 71-94) and accuracy was 79% (CI 69-85). Reversible perfusion abnormalities were detected in > or =2 vascular distributions in 15 of 22 patients with multi-vessel CAD and in 5 of 50 patients without (sensitivity for identifying multivessel CAD=68%, CI 50-89; specificity=90%, CI 82-98; and accuracy=83%, CI 75-90). CONCLUSIONS Stress 99m technetium tetrofosmin myocardial perfusion imaging is a useful non-invasive technique for the diagnosis of in stent stenosis and extent of CAD in patients with previous percutaneous coronary artery interventions.