<jats:p> <jats:bold> <jats:italic>Background and Purpose—</jats:italic> </jats:bold> It is still in debate whether the evaluation of markers of infection and inflammation may be of importance for cerebrovascular and cardiovascular prevention, and we aimed to investigate this field in a prospective 5-year clinical follow-up study in patients with early stages of atherosclerosis. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods—</jats:italic> </jats:bold> We studied 668 subjects divided in 3 groups according to the results of carotid ultrasound examination: (1) normal subjects, if intima-media thickness (IMT) was <0.9 mm; (2) with IMT, if IMT was between 0.9 and 1.5 mm; and (3) with asymptomatic carotid plaque, if IMT was >1.5 mm. Traditional cardiovascular risk factors were investigated, and laboratory analysis included measurement of plasma lipids, fibrinogen, C-reactive protein, IgG antibodies for <jats:italic>helicobacter pylori</jats:italic> (HP), cytotoxic HP, cytomegalovirus, and <jats:italic>chlamydia pneumoniae</jats:italic> . </jats:p> <jats:p> <jats:bold> <jats:italic>Results—</jats:italic> </jats:bold> Cerebrovascular or cardiovascular events were registered in 18% of patients during the follow-up, and at multivariate analysis we found that the high levels of fibrinogen ( <jats:italic>P</jats:italic> <0.0001) and C-reactive protein ( <jats:italic>P</jats:italic> =0.014), the seropositivity to cytotoxic HP ( <jats:italic>P</jats:italic> =0.001) and <jats:italic>chlamydia pneumoniae</jats:italic> ( <jats:italic>P</jats:italic> =0.026), the presence of IMT or asymptomatic carotid plaque ( <jats:italic>P</jats:italic> <0.0001), and the total burden of infections ( <jats:italic>P</jats:italic> <0.0001) were the variables predictive of the clinical events. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> Beyond traditional cardiovascular risk factors, markers of inflammation and infections seem to significantly influence the occurrence of cerebrovascular and cardiovascular events in patients with baseline asymptomatic carotid lesions. </jats:p>