Candidemia studies have documented geographic differences in rates and epidemiology, underscoring the need for surveillance to monitor trends. We conducted prospective candidemia surveillance in Spain to assess the incidence, species distribution, frequency of antifungal resistance, and risk factors for acquiring a Candida infection. Prospective laboratory-based surveillance was conducted from June 2008 to June 2009 in 40 medical centers located around the country. A case of candidemia was defined as the isolation of a Candida species from a blood culture. Incidence rates were calculated per 1,000 admissions. Antifungal susceptibility tests were performed by using broth microdilution assay according to the guidelines of the Clinical and Laboratory Standards Institute. We detected 984 cases, for an overall incidence of 1.09 cases per 1,000 admissions. The crude mortality was 20.20%. Candida albicans was the most common species (49.08%), followed by C. parapsilosis (20.73%), C. glabrata (13.61%), and C. tropicalis (10.77%). Overall, decreased susceptibility to fluconazole occurred in 69 (7.01%) incident isolates. Antifungal resistance was rare, and a moderate linear correlation between fluconazole and voriconazole MICs was observed. This is the largest multicenter candidemia study conducted to date and shows the substantial morbidity and mortality of candidemia in Spain.