Starting in 2010, there was a sharp increase in infections caused by Klebsiella pneumoniae resistant to carbapenems in the Emilia-Romagna region in Italy. A region-wide intervention to control the spread of carbapenemase-producing K. pneumoniae (CPKP) in Emilia-Romagna was carried out, based on a regional guideline issued in July 2011. The infection control measures recommended to the Health Trusts (HTs) were: phenotypic confirmation of carbapenemase production, active surveillance of asymptomatic carriers and contact isolation precautions for carriers. A specific surveillance system was activated and the implementation of control measures in HTs was followed up. A significant linear increase of incident CPKP cases over time (p<0.001) was observed at regional level in Emilia-Romagna in the pre-intervention period, while the number of cases remained stable after the launch of the intervention (p=0.48). Considering the patients hospitalised in five HTs that provided detailed data on incident cases, a downward trend was observed in incidence after the release of the regional guidelines (from 32 to 15 cases per 100,000 hospital patient days). The spread of CPKP in Emilia-Romagna was contained by a centrally-coordinated intervention. A further reduction in CPKP rates might be achieved by increased compliance with guidelines and specific activities of antibiotic stewardship.