Background: Myocardial perfusion imaging by single photon emission computed tomography (MPI–SPECT) is noninvasive test that can give an important information for the diagnosis of coronary artery disease (CAD), detect reversible ischemia, quantify defect sizes and help in clinical decisions of interventions as well as assessment of disease prognosis. Tissue Doppler imaging (TDI) emerged as a potential modality for assessing systolic and diastolic LV performance. Strain doppler echocardiography (SDE) is a new tool for measuring regional myocardial deformation excluding the effect of adjacent myocardial tissue. The development of Instantaneous wave-free Ratio (IFR) as a relatively new invasive method for physiological assessment of coronary lesions without the use of pharmacologic hyperemic agents is the golden standard test for assessment of intermediate coronary lesions and guiding the revascularization decision. Methods: This Cross-sectional study was done was conducted on 50 cases with intermediate coronary artery lesions admitted at the Cardiology departments in Benha University, Kobry Elkobba Military Hospital and Air Force Specialized Hospital. All groups were subjected to history and clinical examination, cardiac examination, 12 lead ECG, 2D echocardiography, routine laboratory investigations, coronary angiography with evaluation of intermediate lesion by IFR then TDI and SDE for evaluation the regional myocardial deformation of the segments supplied by the same coronary artery, after that 99mTc-sestamibi (MIBI) SPECT imaging was done to quantify defect size and finally correlation was done between results of IFR, TDI and SPECT to guide the revascularization decision. Results: Pearson’s correlation analysis showed that; Gated single-photon emission computed moderate and severe Ischemia, Sm-velocity, WMSI, DT, had a highly significant positive correlation with IFR value (p < 0.001). E/A ratio, Mean E/e’ velocity ratio, FS, LVEF and LV GLS had a highly significant negative correlation with IFR value (p < 0.001). Conclusions: Instantaneous wave-free Ratio (IFR) modality is a reliable measure to guide functional significance of the intermediate coronary artery lesions for decision making and guiding plan of management. But it is an expensive and invasive modality. On the other hand, SPECT and tissue doppler modalities showed high sensitivity and specificity in the same group of patients with less expensive, non-invasive and no contrast use advantages.