Cardiac allograft vasculopathy (CAV) is an increasingly important complication after cardiac transplant. We assessed the additive diagnostic benefit of quantitative plaque analysis in patients undergoing coronary computed tomography-angiography (CCTA). Consecutive patients undergoing CCTA for CAV surveillance were identified. Scans were visually interpreted for coronary stenosis. Semiautomated software was used to quantify noncalcified plaque (NCP), as well as its components. Optimal diagnostic cut-offs for CAV, with coronary angiography as gold standard, were defined using receiver operating characteristic curves. In total, 36 scans were identified in 17 patients. CAV was present in 17 (46.0%) reference coronary angiograms, at a median of 1.9 years before CCTA. Median NCP (147 vs 58, P < .001), low-density NCP (median 4.5 vs 0.9, P = .003), fibrous plaque (median 76.1 vs 31.1, P = .003), and fibrofatty plaque (median 63.6 vs 27.6, P < .001) volumes were higher in patients with CAV, whereas calcified plaque was not (median 0.0 vs 0.0, P = .510). Visual assessment of CCTA alone was 70.6% sensitive and 100% specific for CAV. The addition of total NCP volume increased sensitivity to 82.4% while maintaining 100% specificity.NCP volume is significantly higher in patients with CAV. The addition of quantitative analysis to visual interpretation improves the sensitivity for detecting CAV without reducing specificity. K E Y W O R D S cardiovascular disease, clinical research/practice, coronary artery disease, diagnostic techniques and imaging: computed tomography, heart transplantation/cardiology, translational research/science, vasculopathy