The functional significance of coronary artery stenoses of intermediate severity is important in determining strategy in patient care. Intravascular ultrasound (IVUS) is often used to evaluate coronary stenosis severity. However, at present, few data are available about the role IVUS in the assessment of functional significance of intermediate lesions. Myocardial fractional flow reserve (FFR) <0.75 is a reliable index of a functionally severe coronary stenosis. In 53 lesions we assessed (1) by pressure wire: FFR (index of functional significance), and (2) by IVUS: minimal lumen cross-sectional area (MLA, square millimeters), minimal lumen diameter (MLD, millimeters), lesion length (millimeters), and percent area stenosis at the lesion site. By regression analysis, percent area stenosis and lesion length had a significant inverse correlation with FFR (r = -0.58, p <0.001, r = -0.41, p <0.004, respectively). MLD and MLA showed a significant positive relation with FFR (r = 0.51, p <0.001, r = 0.41, p <0.004, respectively). By using a receiver operating characteristic (ROC) curve, we identified a percent area stenosis > 70% (sensitivity 100%, specificity 68%), a MLD < or = 1.8 mm (sensitivity 100%, specificity 66%), a MLA < or =4.0 mm2 (sensitivity 92%, specificity 56%), and a lesion length of >10 mm (sensitivity 41%, specificity 80%) to be the best cut-off values to fit with a FFR <0.75. The combined evaluation of both percent area stenosis and MLD made the IVUS examination more specific (sensitivity 100%, specificity 76%). In 53 intermediate coronary lesions found by angiography, IVUS area stenosis >70%, MLD < or =1.8 mm, MLA < or =4.0 mm2, and lesion length > 10 mm reliably identified functionally critical intermediate coronary stenoses.