Staphylococci account for the bulk of cardiovascular implantable electronic device (CIED) infections. However, a detailed analysis of clinical features and outcomes of CIED infections due to staphylococcal species has not been published. We retrospectively reviewed all cases of CIED infection seen at the Mayo Clinic from 1991 through 2008. Differences in device and host factors, clinical features, and patient outcomes were compared between cases of early and late Staphylococcus aureus and coagulase-negative staphylococci (CoNS) CIED infections. Of 280 cases of staphylococcal CIED infections, 43.9% were due to S. aureus and 56.0% were due to CoNS. Staphylococcus aureus CIED infection cases more frequently involved initially implanted devices. Late S. aureus CIED infection cases compared to late CoNS cases were associated with corticosteroid therapy, hemodialysis, implanted catheters, prosthetic valves, and remote sources of bacteremia. Cases of S. aureus endovascular infections had longer duration of bacteremia (56.0% vs 20.3% ≥3 days), longer hospitalization (37.4% vs 15.2% >20 days), and increased mortality (25.2% vs 9.5%) compared to cases of CoNS endovascular infections (p <0.001 for all comparisons). Overall, CoNS CIED infections compared to S. aureus were associated with a history of multiple device revisions and a higher number of total and abandoned leads at presentation (p <0.001 for all comparisons). In conclusion, CIED infections due to S. aureus and CoNS have distinct clinical features and outcomes.