Controlling the spread of multidrug-resistant bacteria (MDRB) in healthcare facilities is a priority of the National Program for the Prevention of Healthcare-Associated Infections (PROPIAS). Since 2002, the Raisin network has coordinated surveillance of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-producing Enterobacteriaceae) isolated from diagnostic specimens in French HCFs. In 2015, 1,427 HCFs participated in the surveillance program, representing a 199% increase since 2002 and covering 77% of hospital beds in France. For MRSA, the overall incidence rate (IR) was 0.26 per 1,000 patient-days. It was higher in acute care (0.36) and intensive care (0.93) than in long-term care (0.16) and long-term nursing care (0.11). Since 2002, the MRSA ID has decreased by 59% overall and by 63% in intensive care. For E. coli, the overall incidence rate was 0.67 per 1,000 patient-days. It was twice as high in short-stay units (0.93) as in post-surgical care (0.44) and three times as high as in long-term care (0.23). Since 2002, the incidence rate of EBLSE has increased 5.1-fold (+413%), and the proportion of Escherichia coli among EBLSE cases has risen from 19% to 57%. The continued decline in MRSA incidence suggests a positive impact of the prevention measures implemented in the network’s participating units. The annual number of MRSA-related healthcare-associated infections (HAIs) is, however, estimated at between 23,000 and 39,000, including approximately 3,800 to 5,700 bacteremias, and that of EBLSE at between 49,000 and 103,000, including between 5,800 and 10,200 bacteremias. Finally, the increase in the incidence of EBLSE, particularly E. coli, is concerning and may serve as a potential reservoir for the emergence of new carbapenem-resistant strains.