While intravascular imaging guidance during percutaneous coronary intervention (PCI) improves outcomes, routine intravascular imaging usage remains low, in part due to perceived inefficiency and safety concerns.  Aims: The LightLab (LL) Initiative was designed to evaluate whether implementing a standardised optical coherence tomography (OCT) workflow impacts PCI safety metrics and procedural efficiency. In this multicentre, prospective, observational study, PCI procedural data were collected over 2 years from 45 physicians at 17 US centres. OCT-guided PCI incorporating the LL workflow (N=264), a structured algorithm using routine pre- and post-PCI OCT imaging, was compared with baseline angiography-only PCI (angio) (N=428). Propensity score analysis identified 207 matched procedures. Outcomes included procedure time, radiation exposure, contrast volume, device utilisation, and treatment strategy. Compared with angiography alone, LL workflow OCT-guided PCI increased the median procedural time by 9 minutes but reduced vessel preparation time (2 min LL workflow vs 3 min angio; p<0.001) and resulted in less unplanned additional treatment (4% LL workflow vs 10% angio; p=0.01). With LL workflow OCT guidance, fewer cineangiography views were needed compared to angiography guidance, leading to decreased radiation exposure (1,133 mGy LL workflow vs 1,269 mGy angio; p=0.02), with no difference in contrast utilisation between groups (p=0.28). Furthermore, LL workflow OCT guidance resulted in fewer predilatation balloons and stents being used, more direct stent placement, and greater stent post-dilatation than angiography-guided PCI. The incorporation of a standardised pre- and post-PCI OCT imaging workflow improves procedural efficiency and safety metrics, at a cost of a modestly longer procedure time.