A novel substudy of the ILUMIEN-IV trial demonstrates that optical coherence tomography (OCT)-derived virtual flow reserve (VFR) independently predicts 2-year target vessel failure (TVF) after percutaneous coronary intervention (PCI), complementing traditional intravascular imaging-derived anatomic measures, such as minimal stent area (MSA). The findings, published in the Journal of the American College of Cardiology, support the integration of physiology assessment into OCT-guided PCI to optimize procedural outcomes.