Abstract Background Coronary computed tomography angiography (CCTA) provides incremental prognostic information over traditional risk factors in patients with suspected coronary artery disease. However, little is known about the long-term predictive performance of CCTA-derived coronary volumes and mid-diastolic left ventricular (LV) mass. Purpose To assess long-term prognostic value of coronary volumes and mid-diastolic LV mass as novel potential imaging predictors derived from low-dose prospectively ECG-triggered CCTA. Methods Consecutive patients with suspected or known coronary artery disease, referred for low-dose CCTA, were included. Patients with previous revascularization were excluded. The following parameters were evaluated: calcium score, segment involvement score (SIS: 1 point for each coronary segment with presence of plaque), coronary volume, mid-diastolic LV mass and coronary volume indexed to LV mass. Major adverse cardiovascular events (MACE) were defined as all-cause death, non-fatal myocardial infarction and revascularization (PCI or CABG). The association between CCTA measures and the occurrence of events was quantified using cox regression hazard and Kaplan Meier analysis. Results A total of 147 consecutive patients were included in the study. Of them, 93 (63.3%) were male and 79 (53.7%) hat one or more traditional cardiovascular risk factors. There was a weak but statistical significant inverse correlation between indexed coronary volume and both calcium score (R=-0.3, p=0.01) and SIS (R=-0.24, p=0.005). After a median follow-up of 5.8 years 30 MACE occurred in 25 patients, including 3 deaths, 26 revascularizations and 1 non-fatal myocardial infarction. In univariate cox regression hazard analysis calcium score (HR=12.69, 95% CI 2.99–53.83, p<0.001), SIS (HR=1.66, 95% CI 1.43–1.94, p<0.001), LV mass (HR=1.02, 95% CI 1.01–1.03, p=0.007) and indexed coronary volume (HR=0.89, 95% 0.82–0.96, p=0.004) were associated with outcome. In multivariate analysis, indexed coronary volume, remained an independent predictor for MACE when adjusted for traditional risk factors and SIS (HR=0.93, 95% CI 0.87–1.00, p=0.05), while LV mass did not reach statistical significance (p=0.46). By ROC curve analysis, a value of 21.85 mm3/gr was defined as optimal cutoff for indexed coronary volume. In Kaplan Meier plots, patients with low indexed coronary volume (<21.85 mm3/gr) showed higher event rates (log rank p<0.001) compared to high indexed coronary volume (≥21.85 mm3/gr). Conclusions Indexed coronary volume, derived from low-dose CCTA, independently predicts cardiovascular events. Larger studies are mandated to confirm the predictive value of this potential new biomarker.