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The aim of the present study was to evaluate whether computed tomography based-attenuation correction (CT-AC) provides any advantage over non–attenuation-corrected (NAC) images for qualitative and quantitative analysis of single photon emission tomography (SPECT) myocardial perfusion imaging (MPI).We retrospectively evaluated data of 171 patients who underwent stress rest MPI SPECT/CT as per standard protocol. Angiography done within ±3 months of MPI was taken as reference standard. Two readers independently evaluated CT-AC and NAC images. Receiver operating characteristic curve analysis was done using ≥50% and ≥70% stenosis as cutoff. The size and severity of perfusion defects were also compared on CT-AC and NAC images.For both readers, the area under the receiver operating characteristic curve was larger for CT-AC images than for NAC images at both ≥50% and ≥70% cutoff, but the difference was not significant. CT-AC images had significantly lower sensitivity for detecting right coronary artery disease compared with NAC (29% vs. 50% for reader 1 and 25.8% vs. 43.2% for reader 2). However, the specificity improved with CT-AC. Inferior defects were significantly smaller in CT-AC than NAC (P = 0.0002), with no significant difference for anterior defects (P = 0.544). There was significant variation in severity between CT-AC and NAC images for both overall (P = 0.001) as well as for inferior defects (P = 0.0007), but not for anterior defects (P = 0.279).In our study, the CT-based AC improved the specificity but decreased the sensitivity leading to nonsignificant improvement in overall diagnostic accuracy of Tc-99m sestamibi/tetrofosmin MPI.