Antibiotic safety is a major determinant in osteomyelitis therapy. Limited data is available describing the long-term safety and efficacy of daptomycin. the safety population was drawn from CORE 2005 and 2006, a retrospective, observational, multicenter study. Clinically evaluable patients received >3 days of daptomycin appropriately adjusted for renal function. three hundred twenty-seven patients were evaluated for safety; 188 (57%) >or=6 mg/kg, 139 (43%) <6 mg/kg. Thirty-one (10%) patients experienced adverse events possibly related to daptomycin and the incidence was similar regardless of dose. No difference was observed in the rate of creatine phosphokinase elevations by dose. A trend toward higher improved rates was noted in patients receiving a final dose of >or=6mg/kg (96% vs. 90%, P=0.08). Daptomycin appeared well-tolerated at doses of 6 mg per kg or greater which were associated with greater clinical improvement. These results require verification via a prospective clinical trial.