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Background: Coronary artery calcium score (CACS) is widely used for risk stratification. However, in patients with established coronary artery disease, its clinical implication and relationship with plaque vulnerability are unclear. We sought to correlate the CACS and plaque vulnerability assessed by optical coherence tomography., Methods: Patients with coronary artery disease who had CACS and optical coherence tomography before percutaneous coronary intervention were included. Patients were divided into 5 groups based on CACS: CACS of 0, 1 to 99, 100 to 399, 400 to 999, and ≥1000. Optical coherence tomography-derived vulnerable features in culprit plaque were compared between the groups., Results: In 460 patients, the prevalence of lipid-rich plaque, macrophage, and cholesterol crystal significantly differed among the 5 groups, being lowest in the patients with a CACS of 0. The prevalence of thin-cap fibroatheroma tended to be lower in those with a CACS of 0. No significant difference in vulnerable features was observed between the 4 groups with CACS >0. In the 2-group comparison between the group with a CACS of 0 and the other 4 groups combined, the prevalence of lipid-rich plaque (60.5% versus 85.9%; P <0.001), macrophage (48.8% versus 74.1%; P <0.001), thin-cap fibroatheroma (16.3% versus 35.0%; P =0.013), and cholesterol crystal (11.6% versus 32.9%; P =0.004) was significantly lower in the patients with CACS of 0. CACS of 0 was independently negatively associated with lipid-rich plaque, macrophage, thin-cap fibroatheroma, and cholesterol crystal after adjustment for patient characteristics., Conclusions: Patients with a CACS of 0 have a significantly lower prevalence of vulnerable plaque features compared with those with CACS >0 in patients with established coronary artery disease., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194., Competing Interests: Dr Ferencik reports consulting fees from Siemens Healthineers, Elucid, Heartflow, BioMarin, and the Advisory Board of Cleerly and has stock options in Elucid. Dr Jang reports receiving educational grants from Abbott Vascular. The other authors report no conflicts.