The literature indicates that the incidence of invasive fungal infections (IFIs) appears to be on the rise, but few nationwide epidemiological data are available. We analyzed data from the PMSI in metropolitan France between 2001 and 2010 to estimate the incidence and case-fatality rate of the five main IFIs, analyze their trends, and describe their main risk factors (RR). A total of 35,876 new cases were identified (overall incidence: 5.9 cases per 100,000 people per year), including: candidemia (43.3%), pneumocystosis (26.1%), invasive aspergillosis (IA: 23.9%), cryptococcosis (5.2%), and mucormycosis (1.5%). The case-fatality rate was 27.6%. Each year, the incidence of candidemia, IA, and mucormycosis increased by 7.8%, 4.4%, and 7.3%, respectively, while that of pneumocystosis and cryptococcosis decreased by 8.5% and 9.8%, respectively (p<0.05). The incidence of candidemia, AI, and mucormycosis associated with hematologic disorders or cancers increased, while that of pneumocystosis and cryptococcosis associated with HIV/AIDS decreased. For other risk factors, the specific incidence increased: diabetes and candidemia (+8.3% per year), chronic kidney disease and candidemia, AI, or pneumocystosis (+10.3%, +21.0%, and +13.5% per year, respectively), and organ transplants and pneumocystosis (+13.0% per year). This increase in the incidence of IFI prompts a reflection on the necessary changes in patient care. (R.A.)