Coronary computed tomography with myocardial perfusion imaging (CCTA-MPI) provides data on coronary anatomy and perfusion and may be useful in the assessment of ischemic coronary artery disease (CAD). Management of angiographically intermediate coronary lesions is challenging, and coronary fractional flow reserve (FFR) evaluation is recommended to assess whether these lesions are functionally significant. Our aim was to evaluate the diagnostic accuracy of CCTA-MPI in patients with stable CAD and at least 1 angiographically intermediate coronary lesion submitted to FFR. In this single-center prospective study, patients with stable CAD and at least 1 moderate coronary stenosis (50%-70% by visual estimation) were referred for CCTA-MPI (64-row multidetector) assessment before coronary FFR evaluation. Patients with severe coronary obstructions (≥70%) were excluded. The significance level adopted for all tests was 5%. Twenty-eight patients (mean age 60 ± SD years, 54% women) with 33 intermediate coronary obstructions were enrolled. Ten patients (30%) had functionally significant coronary obstructions characterized by FFR ≤0.8. The sensitivity, specificity, and accuracy of CCTA-MPI for the detection of functionally significant coronary obstructions were 30%, 100%, and 78.8%, respectively. CCTA-MPI positive predictive value was 100%, whereas negative predictive value was 76.7%. Correlation coefficient between tests was 0.48 (P = 0.005). On a novel approach to evaluate intermediate coronary lesions, accuracy of CCTA-MPI was 78.8%. The positive predictive value of an abnormal CCTA-MPI on this population was 100%, suggesting that CCTA-MPI may have a role in the assessment of patients with anatomically identified intermediate coronary lesions.