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Although in vitro experimental data and initial sero-epidemiologic, pathology-based studies and antibiotic trials supported this interesting hypothesis, later data are conflicting. Some confounding factors are the causes of uncertainty; lacking of standard methods for &lt;i&gt;C. pneumoniae&lt;\/i&gt; detection, co-existence of other atherosclerotic risk factors and anti-inflammatory effects of antibiotics used in clinical trials seem to be the principal ones. Standardization of methodology used, antibiotic trials with a different orientation-design and a vaccine preparation that eventually will be tested in clinical trials with a long follow-up, should provide a definite answer regarding the probability &lt;i&gt;C. pneumoniae&lt;\/i&gt; to be a main, a secondary or an irrelevant factor to atherosclerosis. 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