OBJECTIVES: Daptomycin is a cyclic lipopeptide antibiotic that has been commercially available in Europe since 2006.  Daptomycin has rapid bactericidal activity against MRSA and is indicated for gram-positive infections including complicated skin and skin structure infections (cSSSI), right-sided infective endocarditis and Staphylococcus aureus bacteremia (BSI).  This study aims to quantify the budgetary impact of utilizing Daptomycin for suspected gram-positive cSSSI and BSI in Germany.  METHODS: A budget impact model was developed to compare the total direct costs of utilizing vancomycin, linezolid, daptomycin, and “other antibiotics” as a single category. A decision tree was constructed on the basis of clinical guidelines and validated by clinicians. Clinical data and laboratory utilization and cost data were derived from a comprehensive review of over 40 publications. Antibiotic utilization and net drug costs were derived using syndicated data from Arlington Medical Resources (AMR).  RESULTS:  On average, the total direct costs (drug acquisition, lab monitoring, and hospital) of treating a cSSSI patient with the following agents were: vancomycin €2598 (4%, 12% and 84%), linezolid €2742 (37%, 5%, and 58%), daptomycin €3,171 (30%, 7%, and 63%), and other antibiotics €1835 (2%, 10%, and 88%). For BSI patients, total direct costs were: vancomycin €2359 (5%, 13% and 82%), linezolid €3951 (37%, 5%, and 58%), daptomycin €2135 (37%, 7%, and 56%), and other antibiotics €3087 (4%, 10%, and 86%). Extrapolating these costs to an average German hospital with 300 BSI and 1000 cSSSI patients and increasing daptomycin use in BSI from 1% to 6% and in cSSSI from 0.3% to 1.4% would save the hospital €30,151 and €2,971 per year, respectively.  CONCLUSIONS:  Using daptomycin for treating cSSSI is budget neutral and using it for bacteremia patients is associated with favorable economic outcomes when compared with other antibiotics.