Micafungin is an echinocandin antifungal agent that has recently been approved for the prevention of invasive fungal infection and the treatment of esophageal candidiasis. Prospective sentinel surveillance for the emergence of in vitro resistance to micafungin among invasive Candida sp. isolates is indicated. We determined the in vitro activity of micafungin against 2,656 invasive (bloodstream or sterile site) unique patient isolates of Candida spp. collected from 60 medical centers worldwide in 2004 and 2005. We performed antifungal susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI) M27-A2 method and used a 24-hour prominent inhibition endpoint for determination of the MIC. Caspofungin was tested in parallel against all isolates. Of 2,656 invasive Candida sp. isolates, species distribution was 55.6% Candida albicans, 14.4% Candida parapsilosis, 13.4% Candida glabrata, 10.1% Candida tropicalis, 2.4% Candida krusei, 1.7% Candida guilliermondii, 0.9% Candida lusitaniae, 0.6% Candida kefyr, and 0.9% other Candida species. Overall, micafungin was very active against Candida (MIC50/MIC at which 90% of the isolates tested are inhibited [MIC90], 0.015/1 microg/ml; 96% inhibited at a MIC of < or =1 microg/ml, 100% inhibited at a MIC of < or =2 microg/ml) and comparable to caspofungin (MIC50/MIC90, 0.03/0.25 mug/ml; 99% inhibited at a MIC of < or =2 microg/ml). Results by species, expressed as MIC50/MIC90 (micrograms per milliliter), were as follows: C. albicans, 0.015/0.03; C. glabrata, 0.015/0.015; C. tropicalis, 0.03/0.06; C. krusei, 0.06/0.12; C. kefyr, 0.06/0.06; C. parapsilosis, 1/2; C. guilliermondii, 0.5/1; C. lusitaniae, 0.12/0.25; other Candida spp., 0.25/1. Although the species distribution varied considerably among the different geographic regions, there was no difference in micafungin activity across the regions. Micafungin has excellent in vitro activity against invasive clinical isolates of Candida from centers worldwide.