This study was conducted to assess clinical and cost outcomes associated with the use of daptomycin. This objective was addressed through a consecutive patient chart review of the first 50 inpatients treated with daptomycin. Type of infection, identity of isolated pathogens, prior therapy, duration of therapy, length of hospitalization, cost of antibiotics, adverse events, and outcomes were evaluated. The analysis showed that mean patient age was 64 y, and mean length of hospitalization was 9.2 d. A total of 62% of patients had confirmed methicillin-resistant Staphylococcus aureus infection. The mean duration of daptomycin therapy was 7.5 d; however, in patients given treatment for complicated skin and skin structure infections, the mean duration of therapy was 6.1 d (n=15) and 7.1 d (n=16) for first- and second-line daptomycin therapy, respectively. The average course of daptomycin cost $727 (n=38) and $390 (n=11), respectively, in the subset of patients with renal insufficiency. In patients who did not respond to prior antibiotic treatment for a Gram-positive bacterial infection (n=26), the mean duration of prior therapy with antibiotics was 6.0 d and the cost was $287. For patients who were transitioned to outpatient daptomycin therapy (n=14), hospital charges were reduced by an estimated $102,340. In 48 patients (96%), infection was resolved with daptomycin therapy. Daptomycin was effective in resolving Grampositive infection in this aged patient population. Earlier identification of antibiotic failure, first-line use of daptomycin in patients with complicated skin and skin structure infections, and outpatient daptomycin therapy provided cost savings and improved clinical outcomes at this facility.