The aim of this study was to describe the clinical experience with daptomycin in the treatment of bacteremia. Patients with a diagnosis of catheter-related or non–catheter-related bacteremia and no other concurrent infection were identified from the Cubicin Outcomes Registry and Experience (CORE) 2004. Treatment success was determined by investigators using protocol criteria and defined as cure or improvement. Of 168 patients with bacteremia, 126 were clinically evaluable. Of those, 52 (41%) patients were aged ≥66 years, 54 (43%) received daptomycin in an intensive care unit, and 25 (20%) had chronic renal failure. The most common pathogens isolated were methicillin-resistant Staphylococcus aureus (33%), vancomycin-resistant enterococci (30%), and coagulase-negative staphylococci (30%). Of 126 patients, 86% received daptomycin after previous antibiotic therapy and most (69%) received concomitant antibiotics with daptomycin. Daptomycin therapy was started at a median dose of 4.0 mg/kg (range, 2.5 to 9.2 mg/kg). Daptomycin therapy had an overall clinical success rate of 89%. Clinical success was independent of baseline renal function, daptomycin dose, pathogen, first-line use, or concomitant antibiotic therapy. These results support the findings of a recent study in which daptomycin was demonstrated to be an effective option in the treatment of S aureus bacteremia. Data in the current study provide insight into the clinical experience using daptomycin to treat bacteremia caused by other gram-positive pathogens. Given the limitations of retrospective studies and lack of follow-up data, additional studies are needed to make definitive evaluations with these pathogens.