In today's cost containment environment it is important to consider changes to standard protocols which would reduce cost, particularly if there is no significant loss of diagnostic accuracy. The aim of the present study was to assess the usefulness of a gated stress-only Tc sestamibi protocol in comparison to conventional gated dual isotope rest-stress myocardial perfusion single photon emission computed tomography (SPECT) in the detection and localization of coronary artery disease (CAD). Sixty-five consecutive patients (65+/-10 years, 22 women) who had undergone conventional gated perfusion SPECT were chosen retrospectively. Fifty-three of these 65 patients had previous coronary arteriography, 45 with at least one stenosis, eight without stenosis, and 12 of these 65 patients had <5% likelihood of CAD. Three readers interpreted the gated stress-only and dual isotope studies in separate sessions blinded to (1). their previous readings, (2). the interpretation by others, and (3). the angiographic results. Readers used a five-point scale to score their visual and quantitative assessment of perfusion, function and compromised vascular territory. Their average score was used for determination of the accuracy by using receiver operating characteristic (ROC) analysis of the techniques. The areas under ROC curves were determined for the detection of CAD and localization of vascular territories. Fifty-four of these patients had 97 significant stress induced perfusion defects as determined by the CEqual quantitative program. The agreement between protocols for the assessment of reversibility in these 97 defects was analysed. There were no statistically significant differences between dual isotope rest/stress and gated stress-only studies for the detection and localization of CAD. The area under the dual isotope rest/stress ROC curve was 0.78+/-0.07 compared to the area under the gated stress-only ROC curve of 0.80+/-0.06, resulting in P=0.30. For the combined vessels comparison of the area under the dual isotope rest/stress ROC curve was 0.73+/-0.04 versus the area under the gated stress-only ROC curve of 0.74+/-0.04, resulting in P=0.27. Similar non-significant differences were obtained when comparing the area under the dual isotope versus gated stress-only ROC curves for the left anterior descending vascular territory (LAD, 0.61+/-0.08 vs 0.660.08, P=0.14), the left circumflex vascular territory (LCX, 0.82+/-0.07 vs 0.81+/-0.06, P =0.47) or the right coronary vascular territory (RCA, 0.80+/-0.06 vs 0.78+/-0.06, P=0.28). The analysis of the reversibility of stress induced perfusion defects yielded a global agreement between protocols of 93% (kappa=0.42). The differences were due to the expert readers, using the gated stress-only protocol, misinterpreting some patients with attenuation artefacts, subendocardial infarction and functional stunning. These results show that the lower cost gated stress-only myocardial Tc myocardial perfusion SPECT studies are comparable to the conventional dual isotope studies when the clinical question is the detection and localization of coronary artery disease. Nevertheless, we also showed that this approach is limited when attempting to interpret the reversibility of stress induced perfusion defects in patients who exhibit attenuation artefacts, subendocardial infarction and functional stunning.