We present a proteomics dataset relying on nanoLC-MS/MS-based shotgun proteomics and using data-independent acquisitions on an Orbitrap hybrid instrument to enable comparisons of protein levels in human carotid endarterectomies with atheromatous plaques, complicated lesions, and healthy vasculature. Study approval, as well as collection and selection of study specimens were described in our previous publication (https://doi.org/https://doi.org/10.1089/ars.2020.8234). Briefly, atherosclerotic samples were obtained from patients by carotid endarterectomies, and healthy carotid arteries (H) were harvested from cadavers of suicide or fatal trauma victims without cardiovascular diseases. All samples were classified by a pathologist according to guidelines by the American Heart Association as atheromatous (A), having complicated lesions (C) and were identical with those having met specified study criteria and included in high-throughput global transcriptomic analyses by RNA-seq earlier. Specifically, inclusion criteria were as follows: samples received within 1 h after endarterectomy, no RNA and protein degradation occurred, blood clot in the artery was absent, and collection of samples was done appropriately. This is a follow up proteomics dataset that used the same samples and the same sample processing protocol but relied on data-dependent acquisition (dataset identifier PXD038922, doi:10.6019/PXD038922). For further comparison, RNA-seq data are also available in the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) database under the accession number PRJNA594843.