AIMS: Segmental pressure gradients post-percutaneous coronary intervention (PCI) can detect residual disease and optimization targets. Ultrasonic flow ratio (UFR) or optical flow ratio (OFR) offer simultaneous physiological and morphological assessment using a single imaging catheter. This study evaluated the utility of UFR and OFR in identifying residual disease post-PCI. METHODS AND RESULTS: The study include patients from the Acetyl Salicylic Elimination Trial JAPAN Pilot study with complete intravascular imaging pullback data, where UFR or OFR was obtained post-PCI. Anatomical focal lesions distal and proximal to the stent were analysed in segments ≥5 mm long. UFR or OFR virtual pullback curves assessed intra-stent pressure gradients, defining physiological focal or diffuse by segmental pressure drops ≥0.05 over lengths <
10 or ≥10 mm, respectively. The median post-PCI UFR/OFR was 0.93 (0.88-0.96) with 35.4% (69/195) vessels having a UFR/OFR <
0.91. There were significantly more focal lesions, both anatomical and physiological, proximal and distal to the stent in vessels with UFR/OFR <
0.91 compared with those ≥0.91. Agreement between anatomical and physiological focal lesions was moderate proximally (kappa = 0.553, CONCLUSION: UFR/OFR effectively identifies sub-optimal vessel physiology post-PCI and locates precise anatomical issues, validated by intravascular imaging. TRIAL REGISTRATION: The ASET JAPAN ClinicalTrials.gov reference: NCT05117866.