Multiple culture and molecular based studies have established the presence of bacteria in atherosclerotic plaques. Although bacteria are present within the plaque, there is no clear understanding or putative pathway as to what part bacteria might play, if any, in the pathogenesis of atherosclerosis. The current models for the pathogenesis of atherosclerotic plaque suggest that persistent infl ammation is an important factor; however, the possible sources for this sustained infl ammation are limited. The concept of biofi lm infection, “a new paradigm of bacterial pathogenesis,” is introduced to show that bacteria, organized into a biofi lm phenotype mode of growth, produces a sustained hyper- infl ammatory host niche. Biofi lm produces an oxidative environment in a host infection. Samples of plaque from 10 patients were examined to compare 16S rDNA to 18S rDNA. Also 4 samples were evaluated in 2 separate locations to evaluate the homogeneity of bacteria within the sample. The 16S rDNA was also sequenced to identify the microorganisms present and their relative contribution to the sample. Several samples demonstrated large amounts of bacterial DNA. The spatial arrangement of bacterial DNA showed a very heterogeneous distribution of bacteria in the plaque. A heat map data analysis shows that for samples that were evaluated in 2 locations the bacteria identifi ed closely correlated. For all the samples combined, the predominant microbial species identifi ed have often been associated with the oral cavity. Several samples show bacterial DNA far exceeding what would be expected by contamination, suggesting the bacteria may be propagating in the plaque. If bacteria are propagating within the plaque, this would most likely be a biofi lm phenotype mode of growth. Biofi lm is known to produce a hyperinfl ammatory response in host environments, and therefore is a candidate for being the “engine” for the persistent infl ammation necessary for the pathogenesis of atherosclerosis.