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To evaluate the accuracy of 64-slice CT angiography (CTA) compared with single photon emission CT (SPECT) myocardial perfusion imaging (MPI), which served as the reference standard, for the detection of functionally significant coronary artery disease (CAD).141 consecutive patients (60 ± 10 years, 101 men) were investigated with 64-slice CTA and SPECT MPI; a subset of 35 patients had additional invasive coronary angiography (ICA). The data from CTA and ICA were compared with those from MPI for both cut-offs of ≥ 50% and ≥ 70% stenosis, respectively.The sensitivity, specificity, positive and negative predictive values, and accuracy of CTA, using a cut-off of ≥ 50% for significant stenosis, in detecting inducible perfusion defects on MPI were 96% [95% confidence interval (CI) 88-100%], 61% (95% CI 52-70%), 37% (95% CI 23-49%), 99% (95% CI 97-100%) and 68%, respectively, in patient-based analysis and 97% (95% CI 91-100%), 86% (95% CI 83-89%), 33% (95% CI 24-42%), 100% (95% CI 99-100%) and 87%, respectively, in vessel-based analysis. Applying a cut-off of ≥ 70% for significant stenosis, CTA yielded the following sensitivity, specificity, positive and negative predictive values, and accuracy for the detection of inducible MPI defects: by patient, 65% (95% CI 46-84%), 95% (95% CI 91-99%), 74% (95% CI 50-92%), 92% (95% CI 87-97%) and 89%, respectively; by vessel, 58% (95% CI 42-74%), 97% (95% CI 95-99%), 62% (95% CI 45-79%), 97% (95% CI 95-99%) and 95%, respectively.64-slice CTA is a reliable tool to exclude functionally significant CAD when using a cut-off of ≥ 50% diameter stenosis. By contrast, a cut-off of ≥ 70% diameter narrowing is a strong predictor of ischaemia.