For a study, the researchers sought to determine if coronary computed tomographic angiography (CCTA) derived unfavorable geometric characteristics (AGCs) of coronary lesions, including location and vascular geometry, contribute to plaque shape and burden and could be used to identify culprit lesion precursors linked to future acute coronary syndrome (ACS). Patients with ACS and a culprit lesion precursor detected on baseline CCTA (n=116) and propensity score-matched non-ACS controls (n=116) were enrolled in the substudy of ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a multicenter nested case-control cohort study. Data was collected between July 20, 2012, and April 30, 2017, with analysis taking place between October 1, 2020, and October 31, 2021. In 116 patients, 116 culprit lesion precursors were found out of 548 lesions (80 [69.0%] men; mean [SD], age 62.7 [11.5] years). The distance between the ostium and the precursors of culprit lesions was shorter (median, 35.1 [IQR, 23.6-48.4] mm vs 44.5 [IQR, 28.2-70.8] mm), they were more frequently localized to bifurcations (85 [73.3%] vs 168 [38.9%]), and they had more tortuous vessel segments (5 [4.3%] vs 6 [1.4%]; all P<.05). In a multivariate Cox regression analysis, having more AGCs was linked to a higher risk of future culprit lesions (hazard ratio [HR] for 1 AGC, 2.90 [95% CI, 1.38-6.08]; P=.005; HR for ≥2 AGCs, 6.84 [95% CI, 3.33-14.04]; P<.001). When added to a model that included stenosis severity, adverse morphological plaque features, and quantitative plaque characteristics, adverse geometric characteristics gave incremental discriminating value for culprit lesion precursors (area under the curve, 0.766 [95% CI, 0.718-0.814] vs 0.733 [95% CI, 0.685-0.782]). When compared to control patients, patients with ACS had a higher frequency of lesions with adverse plaque characteristics, AGCs, or both (≥2 adverse plaque characteristics, 70 [60.3%] vs 50 [43.1%]; ≥2 AGCs, 92 [79.3%] vs 60 [51.7%]; ≥2 of both, 37 [31.9%] vs 20 [17.2%]; all P<.05). The outcomes back up the theory that CCTA-derived AGCs that capture lesion site and vascular geometry were linked to the risk of ACS-causing culprit lesions in the future. In addition to plaque assessment in CCTA, adverse geometric aspects may provide additive prognostic information.