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In Greece, there are high rates of methicillin (40%–60%) and clindamycin (15%–25%) resistance among community-acquired Staphylococcus aureus isolates. Therefore, we sought to identify other antimicrobial treatment options such as daptomycin.We studied retrospectively all pediatric infections treated with daptomycin at the University General Hospital of Larissa, Greece, from January 1, 2007, to June 16, 2016.Of a total of 128 patients (median age: 2.8 years; range: 8 days to 14.5 years; 76.6% <7 years) treated with daptomycin, 45 (35.2%) had invasive infection, most frequently musculoskeletal, and 83 (64.8%) had noninvasive infection, that is, complicated skin and soft tissue infection. S. aureus was the most commonly recovered pathogen (n = 61) (63.9% methicillin-resistant isolates, 21.3% clindamycin-resistant). The average daily dose of daptomycin was 10 mg/kg qd, and the median duration of therapy was 10 days. Daptomycin was administered alone (n = 61) or in combination therapy (n = 67), most frequently with rifampin (n = 40) and/or a β-lactam antibiotic (n = 33). Open or closed drainage was performed in 86 (67.2%) of the total number of patients. Of 128 treated patients, 123 (96.1%) achieved clinical success, 114 (89.1%) had complete remission, and 9 (7%) had improvement of their disease. There were no failures with daptomycin therapy. The adverse events were of no clinical significance.Daptomycin administered alone or in combination with other antimicrobial agents to children was efficacious and well tolerated in the treatment of complicated infections of suspected or proven staphylococcal etiology.