Meticillin-resistant Staphylococcus aureus (MRSA) disseminates between hospitals serving one patient catchment area. Successful prevention and control requires concerted efforts and regional surveillance. Forty hospitals located in the German EUREGIO have established a network for combating MRSA. In 2007 they agreed upon a synchronised strategy for screening of risk patients and a standard for transmissionbased precautions (search and follow). The same year, the hospitals started synchronised MRSA prevention and annually reporting MRSA-data to the public health authorities. The median rate of screening cultures per 100 patients admitted increased from 4.38 in 2007 to 34.4 in 2011 (p<0.0001). Between 2007 and 2011, the overall incidence density of MRSA (0.87 MRSA cases/1,000 patient days vs 1.54; p<0.0001) increased significantly. In contrast, both the incidence density of nosocomial MRSA cases (0.13 nosocomial MRSA cases/1,000 patient days in 2009 vs 0.08 in 2011; p=0.0084) and the MRSA-days-associated nosocomial MRSA rate (5.51 nosocomial MRSA cases/1,000 MRSA days in 2009 vs 3.80 in 2011; p=0.0437) decreased significantly after the second year of the project. We documented adherence to the regional screening strategy resulting in improved detection of MRSA carriers at admission. Subsequently, after two years the nosocomial MRSA-incidence density was reduced. Regional surveillance data, annually provided as benchmarking to the regional hospitals and public health authorities, indicated successful prevention.