Aims The aim of this study was to determine the diagnostic performance of single-photon emission computed tomography (SPECT), stress echocardiography (SE), invasive coronary angiography (ICA), coronary computed tomography angiography (CCTA), fractional flow reserve (FFR) derived from CCTA (FFRCT), and cardiac magnetic resonance (MRI) imaging when directly compared with an FFR reference standard. Method and results PubMed andWeb of Knowledge were searched for investigations published between 1 January 2002 and 28 February 2015. Studies performing FFR in at least 75% of coronary vessels for the diagnosis of ischaemic coronary artery disease (CAD) were included. Twenty-three articles reporting on 3788 patients and 5323 vessels were identified. Meta-analysis was performed for pooled sensitivity, specificity, likelihood ratios (LR), diagnostic odds ratio, and summary receiver operating characteristic curves. In contrast to ICA, CCTA, and FFRCT reports, studies evaluating SPECT, SE, and MRI were largely retrospective, single-centre and with generally smaller study samples. On a per-patient basis, the sensitivity of CCTA (90%, 95% CI: 86-93), FFRCT (90%, 95% CI: 85-93), and MRI (90%, 95% CI: 75-97) were higher than for SPECT (70%, 95% CI: 59-80), SE (77%, 95% CI: 61-88), and ICA (69%, 95% CI: 65-75). The highest and lowest perpatient specificity was observed for MRI (94%, 95% CI: 79-99) and for CCTA (39%, 95% CI: 34-44), respectively. Similar specificities were noted for SPECT (78%, 95% CI: 68-87), SE (75%, 95% CI: 63-85), FFRCT (71%, 95% CI: 65-75%), and ICA (67%, 95% CI: 63-71). On a per-vessel basis, the highest sensitivity was for CCTA (pooled sensitivity, 91%: 88-93), MRI (91%: 84-95), and FFRCT (83%, 78-87), with lower sensitivities for ICA (71%, 69-74), and SPECT (57%: 49-64). Per-vessel specificity was highest for MRI (85%, 79-89), FFRCT (78%: 78-81), and SPECT (75%: 69-80), whereas ICA (66%: 64-68) and CCTA (58%: 55-61) yielded a lower specificity. Conclusions In this meta-analysis comparing cardiac imaging methods directly to FFR, MRI had the highest performance for diagnosis of ischaemia-causing CAD, with lower performance for SPECT and SE. Anatomic methods of CCTA and ICA yielded lower specificity, with functional assessment of coronary atherosclerosis by SE, SPECT, and FFRCT improving accuracy.