Combination of both morphological and functional information has gained more and more appreciation with the concept of "functionally relevant coronary artery lesion (FRCAL)" and "functional revascularization". This has paved the way for non-invasive single-photon emission computed tomography (SPECT)/computed tomography angiography (CTA) hybrid imaging. We aimed at assessing the value of cardiac hybrid imaging on the detection of FRCAL and its potential as a gatekeeper for invasive examination and treatment. In Two hundred and thirty-eight patients with known or suspected coronary artery disease (CAD) underwent CTA and myocardial perfusion imaging (MPI) using SPECT on a dual system scanner in one session before treatment. 78 patients underwent invasive coronary angiography (CAG) within 1 month. Detection of FRCAL by the combination of SPECT/CTA was compared with SPECT/CAG, which served as a standard of reference. According to the both combination results, treatment decision (revascularization or medical treatment) was chosen in the catheterization laboratory. Sensitivity, specificity, accuracy, positive and negative prediction rate by SPECT/CTA vs. SPECT/CAG for the detection of flow-limiting coronary stenosis on patient- and vessel-based analysis were 94.33, 72.00, 87.18, 87.71, 85.71 % and 88.71, 92.44, 91.45, 80.89, 95.78 %, respectively. No revascularization procedures were performed in patients without flow-limiting stenosis. However, more than one-third (25/67, 37 %) of revascularized vessels were not associated with ischemia on MPI. The cardiac SPECT/CTA hybrid imaging can accurately detect FRCAL and thereby it may be used as a gatekeeper for CAG and revascularization procedures.