Abstract Aims Adverse plaque characteristics determined by coronary computed tomography angiography (CTA) have been associated with future cardiac events. Our aim was to investigate whether quantitative global per-patient plaque characteristics from coronary CTA can predict subsequent cardiac death during long-term follow-up. Methods and results Out of 2748 patients without prior history of coronary artery disease undergoing CTA with dual-source CT, 32 patients suffered cardiac death (mean follow-up of 5 ± 2 years). These patients were matched to 32 controls by age, gender, risk factors, and symptoms (total 64 patients, 59% male, age 69 ± 10 years). Coronary CTA data sets were analysed by semi-automated software to quantify plaque characteristics over the entire coronary tree, including total plaque volume, volumes of non-calcified plaque (NCP), low-density non-calcified plaque (LD-NCP, attenuation <30 Hounsfield units), calcified plaque (CP), and corresponding burden (plaque volume × 100%/vessel volume), as well as stenosis and contrast density difference (CDD, maximum percent difference in luminal attenuation/cross-sectional area compared to proximal cross-section). In patients who died from cardiac cause, NCP, LD-NCP, CP and total plaque volumes, quantitative stenosis, and CDD were significantly increased compared to controls (P < 0.025 for all). NCP > 146 mm³ hazards ratio (HR) 2.24; 1.09–4.58; P = 0.027, LD-NCP > 10.6 mm³ (HR 2.26; 1.11–4.63; P = 0.025), total plaque volume > 179 mm³ (HR 2.30; 1.12–4.71; P = 0.022), and CDD > 35% in any vessel (HR 2.85;1.4–5.9; P = 0.005) were associated with increased risk of future cardiac death, when adjusted for segment involvement score. Conclusion Among quantitative global plaque characteristics, total, non-calcified, and low-density plaque volumes as well as CDD predict cardiac death in long-term follow-up.