In 2006 and 2007, a large outbreak of Clostridium difficile infections (CDIs) with PCR-ribotype 027 was identified in northern France. Overall, 38 healthcare facilities notified 529 CDIs over a 22-month period, including 281 laboratory-confirmed CDI 027 and 248 non-confirmed CDI 027 cases (incidence rate per 10,000 elective bed days: 1.63, range: 0.07 to 7.94). The cases occurred mainly in long-term care hospital facilities and nursing homes, near the border between France and Belgium. An active surveillance and prevention campaign was launched at the first epidemic peak including hygiene precautions for healthcare professionals, which supported healthcare facilities to improve care organisation. The outbreak was controlled at the end of 2007, but sporadic cases were identified until the end of 2009. A bundle of appropriate control measures may halt the spread of such outbreaks, provided that substantial human resources and financial support are available.