In 2001, health authorities made it mandatory to report rare or serious healthcare-associated infections (HAIs) in order to detect them early and facilitate their control. We describe the events detected by this system from August 2001 to December 2005. These are isolated or clustered cases of HIs reported by healthcare facilities (HCFs) to the Coordination Centers for the Control of Healthcare-Associated Infections, the Departmental Directorate of Health and Social Affairs, and the French Institute for Public Health Surveillance if they meet certain criteria related to the microorganism (virulence or resistance), the site of infection, the severity of the infection, or its mode of transmission. From 2001 to 2005, 3,110 reports totaling 9,322 infections were received from 787 HCFs; 755 (24%) corresponded to clustered cases. The number of reports increased steadily from 2001 to 2005, but reporting rates varied by type of healthcare facility and region. The most frequently reported microorganisms were Staphylococcus aureus (16% of reports), Enterobacteriaceae (12%), Acinetobacter baumannii (10%), and Pseudomonas aeruginosa (7.5%). The reporting system identified recurrent NI (hepatitis C, aspergillosis, invasive Group A streptococcal infections, endophthalmitis, or iatrogenic meningitis). It also enabled the detection of rare infections (Enterobacter sakazakii) or emerging infections (multidrug-resistant bacteria such as vancomycin-resistant enterococci, certain strains of Acinetobacter baumannii, or Klebsiella pneumoniae). Due to their potential international impact, three events were reported to European Union member states. The reporting of NI in France has facilitated the investigation and control of NI. By identifying certain high-risk practices, it has helped strengthen prevention recommendations. The system’s ability to rapidly detect and control outbreaks depends on the commitment of healthcare professionals and the responsiveness of coordination and expert bodies. (R.A.)