To evaluate the ability of minimal luminal area (MLA) measured by intravascular ultrasound (IVUS) to assess the functional significance of coronary artery disease. The use of IVUS to determine the functional significance of coronary artery lesions remains a matter for debate. From our prospective IVUS imaging database between July 2009 and April 2010, 170 coronary lesions in 150 patients who underwent stress myocardial single-photon emission computed tomography (SPECT) performed within 1 month of IVUS evaluation were identified and analyzed. MLA and other parameters were measured by IVUS and compared with the results of myocardial SPECT. Overall, 45 lesions had positive SPECT; and 125 lesions had negative SPECT. The MLA of lesions with positive SPECT was smaller than those with negative SPECT (1.7짹0.5mm2 vs. 2.3짹1.1mm2, p<0.001). By logistic regression analysis, MLA (odd ratio 3.1, 95% CI 1.75-5.5, p<0.01) was an independent predictor of the positive SPECT. Using receiver-operating curve analysis, best cut-off value of MLA was ���2.1mm2 with a 86.7% sensitivity, a 50.4% specificity, a 38.6% positive predictive value, and a 91.3% negative predictive value versus lesions with a positive SPECT (area under curve 0.690 [95% CI 0.615- 0.759], p<0.01). In conclusions, the best cut-off value of MLA measured by IVUS to predict myocardial ischemia was 2.1mm2. Nevertheless, the IVUS measured MLA appeared to play a limited role in detecting functionally significant lesions assessed by myocardial perfusion scan.