This study sought to compare how the tissue extracellular vesicle proteome of carotid atherosclerotic plaques differs between symptomatic and asymptomatic patients. Carotid arteries samples were collected from symptomatic and asymptomatic patients undergoing endarterectomies. The specimen was grossly dissected in to 1) the maximally diseased plaque zone and 2) adjacent marginal zones. Extracellular vesicles were isolated from these matched tissue regions from each specimen using collagenase digestion, size exclusion chromatography, and density gradient ultracentrifugation. Label-free proteomics was performed on both the intact tissues (N=5) and the tissue derived EVs (N=23: symptomatic patients N=13, asymptomatic patients N=10).