Cardiovascular disease presents significant variations in human populations with respect to the atherosclerotic plaque progression, inflammation, thrombosis and rupture. In order to gain a more comprehensive picture of the pathogenic mechanism of atherosclerosis and the variations seen in patients, efficient methods to identify proteins from the normal and diseased arteries need to be developed. To accomplish this goal, we tested the feasibility and efficiency of protein identification by a recently developed method, termed the direct tissue proteomics (DTP). We analyzed frozen and paraformaldehyde-fixed archival coronary arteries with the DTP method. We also validated the distinct expression of four proteins by immunohistochemistry (IHC). In addition, we demonstrated the compatibility of the DTP method with laser capture microdissection (LCM) and the possibility of monitoring specific cytokines and growth factors by the absolute quantification of abundance (AQUA) method. Major findings from this feasibility study are that 1) DTP can be used to efficiently identify proteins from paraformaldehyde-fixed, paraffin embedded and frozen coronary arteries, 2) approximately twice the number of proteins were identified from the frozen sections when compared to the paraformaldehyde-fixed sections, 3) LCM is compatible with the DTP, and 4) detection of low abundant cytokines and growth factors in the coronary arteries required selective reaction monitoring experiments coupled to AQUA. The analysis of 35 human coronary atherosclerotic samples allowed identification of a total of 806 proteins. The present study provides the first large-scale proteomic map of human coronary atherosclerotic plaques.