Abstract Background The segment involvement score (SIS) is a semiquantitative measure of the extent of atherosclerosis burden by coronary computed tomography angiography (-CTA). We sought to evaluate by meta-analysis the prognostic value of SIS, and to compare it with other CTA measures of coronary artery disease (CAD). Methods Electronic databases from 1946 to January 2016 were searched. Studies reporting SIS, or an equivalent measure by coronary CTA, and clinical outcomes were included. Maximally adjusted hazard ratios (HR), predominantly for clinical variables, were extracted for SIS, obstructive CAD, Agatston coronary artery calcium score, and plaque composition. These were pooled using DerSimonian-Laird random effects models. Results Eleven nonrandomized studies with good methodological quality enrolling 9777 subjects (mean age 61 ± 11 years, 57% male, mean follow up 3.3 years) who had 472 (4.8%) MACE (cardiac or all cause death, non-fatal myocardial infarction or late revascularization), were included. SIS (per segment increase) had pooled HR of 1.25 (95% CI: 1.16,1.35; I2  = 71.4%, p < 0.001) for MACE. HR for MACE was 1.37 (95% CI: 1.32,1.42; I2  = 95.6%, p < 0.001) for number of segments with stenosis (per segment increase), 3.39 (95% CI: 1.65,6.99; I2  = 87.8%, p = 0.001) for obstructive CAD (binary variable) and 1.00 (95% CI: 1.00,1.01; I2  = 75.0%, p = 0.490) for Agatston score (per unit increase). HRs by plaque composition (calcified, non-calcified and mixed; per segment change) were 1.24 (95% CI: 1.10,1.39; I2  = 81.6%, p = 0.001), 1.20 (95% CI: 0.97,1.48; I2  = 92.9%, p = 0.093) and 1.27 (95% CI: 1.03,1.58; I2  = 89.8%, p = 0.029), respectively. Conclusion Despite heterogeneity in endpoints, extent of CAD as quantified by SIS on coronary CTA is a strong, independent predictor of cardiovascular events.