Objectives. The rate of infection in patients who require ventricular assist devices (VADs) is estimated at more than 35%. Infections with multidrug-resistant (MDR) organisms in VAD recipients present a high mortality rate. Daptomycin (Cubicin, Novartis, Nuremberg, Germany), a new cyclic lipopeptide antibiotic, is useful for MDR gram-positive organisms. We report the successful use of daptomycin in patients presenting with MDR gram-positive infections after VAD implantation. Methods. We retrospectively studied nine consecutive patients presenting with resistant gram-positive infections after VAD implantation treated with daptomycin. We analyzed type of VAD, type of infection, responsible microorganism, outcome, and adverse events. Results. We studied nine patients (eight males, one female), of overall mean age of 51 +/- 8 years; 78% required a biventricular assist device or a left VAD (Berlin Heart, Berlin, Germany), 22% received other ventricular support. Sixty-six percent presented with catheter-related infections (CRIs). Therapy with daptomycin was empirically initiated in all cases. The initial dose was 6 mg/kg, continued at 4 mg/kg. The mean duration of therapy was 16 5 days. The reported pathogens were MRSA, 33%; E. faecium, 25%; methicillin-resistant staphylococcus epidermidis, 12.5%; methicillin-sensitive staphylococcus aureus, 12.5%; others, 17%. Successful outcomes were reported in seven subjects (78%), with two patients succumbing due to multiorgan failure related to their heart condition prior completing antibiotic therapy. No adverse events were reported. Conclusions. Among our VAD patients, daptomycin proved efficient as a therapy for CRI with bacteremia. However, controlled studies are necessary to evaluate this antibiotic in patients presenting with VAD and MDR bacteremia.