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Luminal stenosis, computed-tomography derived fractional-flow reserve (FFRCT), and high-risk plaque features on coronary computed tomography angiography (CCTA), are all known to be associated with adverse clinical outcomes. To assess the interactions between these variables, patient outcomes, and quantitative plaque volumes, have not been previously described. Patients with CCTAs (n=4,430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry underwent AI enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume (TPV) and each plaque subtype were derived using ROC analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFRCT, and translesional delta-FFRCT. Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events (MACE), late revascularization, a composite of the two, and cardiovascular death & myocardial infarction (MI). At one-year, 55 patients (1.2%) had experienced MACE, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis and FFRCT, TPV above the ROC-derived optimal cutoff (TPV > 564 mm3) was associated with the MACE/late revascularization composite (adjusted HR 1.515, 95%CI 1.093-2.099, p=0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both MACE/late revascularization (TPAV >24.4%, HR 2.046, 95%CI 1.474-2.839, p<0.0001) and cardiovascular death/MI (TPAV >37.17%, HR 4.53, 95%CI 1.943-10.576, p=0.0005). Calcified, non-calcified and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/MI in analyses stratified by median plaque volumes. Analysis of the ADVANCE registry using AI-enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFRCT. [ABSTRACT FROM AUTHOR]