BACKGROUND Staphylococcus aureus bacteremia (SAB) in patients with cardiovascular implantable electronic devices (CIED), including permanent pacemakers (PPMs) and implantable cardioverter-defibrillators (ICD), can be the sole manifestation of device infection. METHODS To assess clinical factors associated with CIED infection, we retrospectively reviewed all patients with both CIED and SAB seen at Mayo Clinic Rochester between 2001 through 2006. CIED infection was defined using microbiological and clinical criteria. RESULTS Of the 62 patients with SAB and a CIED, 22 patients (35.5%) had CIED infection. The generator pocket was identified as the source of bacteremia in seven (11%) patients. The majority of CIED infections were device-related infective endocarditis (12 of 22, 55%). Thirty percent of patients presenting with SAB greater than 1 year after device implantation had CIED infection; all but one had CIED-related infective endocarditis. Sixty percent of ICD patients (12 of 20) with SAB had CIED infection, compared with 24% of PPM patients (10 of 42, P = 0.01). On univariate analysis factors associated with CIED-related infective endocarditis included device type [odds ratio (OR) for ICD 13.3, 95% confidence interval [CI] 2.1, 84.9) and presence of a prosthetic heart valve (OR 6.8 95% CI 1.1, 43.4). CONCLUSIONS CIED infection is common in patients with SAB. The presence of an ICD and prosthetic heart valve were associated with CIED-related infective endocarditis. Subsequent work should focus on prospectively characterizing the subset of patients with CIED infection who present with SAB as the sole manifestation of their device infection. (PACE 2010; 407-413).