Abstract Background The prognostic significance of coronary plaque localization, percentage atheroma volume (PAV), stenosis, and plaque morphology has been underexplored. Purpose To investigate the prognostic significance of plaque localization beyond plaque burden, presence of stenosis and plaque morphology. Methods Patients with no cardiac history who underwent coronary CTA were included. PAV, maximum diameter stenosis, and plaque morphology were assessed and classified into proximal, mid, or distal segments of the coronary tree. Major adverse cardiac events (MACE) were defined as death or non-fatal myocardial infarction. Results Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. PAV of the proximal segments was strongly correlated to PAV localized at of the mid (R= 0.76) and distal segments (R = 0.74, p < 0.01 for both). When adjusted for traditional risk factors and presence of plaque on other locations, only proximal PAV was independently associated with MACE (3rd quartile HR 2.08, 95% 1.17–3.71, p=0.01 and 4th quartile HR 2.29, 95% CI 1.21–4.34, p=0.01). Similar results were seen for presence of stenosis. Proximal, mid, and distal PAV as a solitary metric (unadjusted) had similar predictive value for MACE with an AUC of 0.73 (95% CI 0.69-0.76) for proximal PAV and 0.72 (95% CI 0.68-0.76) for both mid and distal localized plaque). Similar results were obtained using diameter stenosis instead of PAV. The presence of low-attenuation plaque (LAP) in the proximal segments had additional prognostic value. Calcified or noncalcified PAV did not provide additional value beyond total location-specific PAV and presence of low-attenuation plaque. Conclusions Proximal located PAV is an independent predictor of death and non-fatal MI, while there was no incremental prognostic value of plaque localized at the mid or distal coronary segments. The presence of LAP in the proximal segments provided additional prognostic value for prediction of MACE.