This study was to evaluate the loading does of daptomycin, a novel lipopeptide antibacterial active against Gram-positive pathogens, on clinical efficiency. We divided patients received daptomycin therapy into 2 groups. One of two groups comprised patients received the loading dose of daptomycin on day 1 (group 1) and the other group received normal dosage (4-6mg/kg/day) (group 2). Inflammatory markers were assessed at least 3 days before daptomycin therapy started as their baseline, and 2 weeks from daptomycin therapy started for the evaluation of clinical efficacy. The bacteriological results were also evaluated. The occurrence of creatinine kinase (CK) elevation was evaluated as side effect. As results, the only group 1 showed significant improvements in body temperature and CRP on 4-7 days after daptomycin therapy started, while 2 groups significantly improved in WBC, body temperature and CRP on 8-14 days, respectively. The group 1 showed early improvement of body temperature (<37.5°C) on 4-7 days, compared with the group 2 (group 1; 3 [2-7], group 2; 6 [2-11], p=0.01). The bacteriological cure rates in both groups showed high cure rates (group 1; 20/0, group 2; 27/3, p=0.14). The frequency of CK elevation was 0% (0/22 patients) and 3.0% (1/33 patients) in group 1 and group 2, respectively. In our conclusion, daptomycin loading dose did not prove evident clinical effectiveness, compared with the regimen without loading dose. However, we could not disclaim the potential to improve clinical response early with DAP loading dose for critically ill patients.