A prospective study was conducted over a 3-year period (2005–2007) in 12 French university hospitals to identify cases of confirmed or probable invasive aspergillosis (IA). Cases were reported by mycologists following application of the EORTC/MSG criteria; the number of hospital admissions and transplants was obtained from national registries. A total of 424 patients were included, representing a median incidence of 0.271 per 100 admissions (range: 0.072–0.910), with no seasonal variations or variations by study year. Among the 393 adults (62% male, mean age 56 years), 78% had an underlying hematologic disease, 15% had proven AI, and 92% had pulmonary involvement. Acute leukemias (34.6%) and allogeneic stem cell transplants (21.4%) were the main risk factors, followed by chronic lymphoproliferative syndromes (21.6%), which are emerging as a new risk group. Other risk factors included solid organ transplants (8.7%), solid malignant tumors (4.3%), systemic inflammatory diseases (4.6%), and chronic respiratory conditions (2.3%). Positive cultures (n=245) confirmed the predominance of Aspergillus fumigatus (pure culture=80%). Serum galactomannan testing was more frequently positive (69%) in hematology than in other conditions (<42%; p<0.001). As first-line treatment, voriconazole alone was most commonly prescribed (52%), followed by antifungal combinations (19.9%), caspofungin (14%), and a lipid-based formulation of amphotericin B (8%). Overall mortality at 12 weeks was 44.8%; it was 41% when first-line treatment included voriconazole versus 60% otherwise (p<0.001). Advanced age, a positive fungal culture combined with a positive galactomannan test, and central nervous system involvement or pleural effusion were independent predictors of 12-week mortality, whereas treatment including at least voriconazole appeared to be protective. (R.A.)