Aortoiliac and lower extremity arterial atherosclerotic plaque burden is a risk factor for the development of visceral and peripheral ischemic and aneurismal vascular disease. While prior research allows automated quantification of calcified plaque in these body regions using CT angiograms, no automated method exists to quantify soft plaque. We developed an automatic algorithm that defines the outer wall contour and wall thickness of vessels to quantify non-calcified plaque in CT angiograms of the chest, abdomen, pelvis, and lower extremities. The algorithm encodes the search space as a constrained graph and calculates the outer wall contour by deriving a minimum cost path through the graph, following the visible outer wall contour while minimizing path tortuosity. Our algorithm was statistically equivalent to a reference standard made by two reviewers. Absolute error was 1.9 ± 2.3% compared to the inter-observer variability of 3.9 ± 3.6%. Wall thickness in vessels with atherosclerosis was 3.4 ± 1.6 mm compared to 1.2 ± 0.4 mm in normal vessels. The algorithm shows promise as a tool for quantification of non-calcified plaque in CT angiography. When combined with previous research, our method has the potential to quantify both non-calcified and calcified plaque in all clinically significant systemic arteries, from the thoracic aorta to the arteries of the calf, over a wide range of diameters. This algorithm has the potential to enable risk stratification of patients and facilitate investigations into the relationships between asymptomatic atherosclerosis and a variety of behavioral, physiologic, pathologic, and genotypic conditions.