BACKGROUND: The relationship between fractional flow reserve (FFR), resting full-cycle ratio (RFR), instantaneous wave-free ratio (iFR), resting distal pressure/aortic pressure (Pd/Pa), and plaque burden as well as phenotype requires further elucidation. METHODS AND RESULTS: In this single-center cohort study, patients with suspected coronary artery disease who underwent invasive coronary angiography, including routine hyperemic (FFR) and nonhyperemic invasive pressure (Pd/Pa and iFR or RFR) interrogation and computed coronary tomography angiography were prospectively enrolled. Computed coronary tomography angiography was used to assess percentage atheroma volume (PAV), positive remodeling, and low-attenuation plaque. Among 241 patients with 556 vessels, FFR correlated stronger to PAV compared with Pd/Pa (r=−0.56; versus r=−0.43; P<0.01) and iFR/RFR (r=−0.47; P=0.04). Vessels with FFR and Pd/Pa discordancy showed higher PAV in case of abnormal FFR (34% versus 14%; P<0.01), whereas vessels with FFR and iFR/RFR discordancy showed similar PAV levels. FFR and iFR/RFR, but not Pd/Pa, were independently associated with the presence of low-attenuation plaque (β, −0.03, P<0.01; β, −0.03, P=0.01; and β, −0.02, P=0.10, respectively). None of the invasive pressure measurements was independently associated with positive remodeling. Pressure index discordancy was not associated with positive remodeling or low-attenuation plaque. CONCLUSIONS: FFR correlated stronger to plaque burden, as defined by PAV, than nonhyperemic pressure indexes. For plaque phenotype, both FFR and iFR/RFR were independently associated with low-attenuation plaque, whereas none of the invasive pressure indexes was associated with positive remodeling.