Introduction: Meticillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections. Aim: We describe MRSA colonisation/infection and bacteraemia rate trends in Dutch-German border region hospitals (NL-DE-BRH) in 2012-16. Methods: All 42 NL-DE BRH (8 NL-BRH, 34 DE-BRH) within the cross-border network EurSafety Health-net provided surveillance data (on average ca 620,000 annual hospital admissions, of these 68.0% in Germany). Guidelines defining risk for MRSA colonisation/infection were reviewed. MRSA-related parameters and healthcare utilisation indicators were derived. Medians over the study period were compared between NL- and DE-BRH. Results: Measures for MRSA cases were similar in both countries, however defining patients at risk for MRSA differed. The rate of nasopharyngeal MRSA screening swabs was 14 times higher in DE-BRH than in NL-BRH (42.3 vs 3.0/100 inpatients; p <0.0001). The MRSA incidence was over seven times higher in DE-BRH than in NL-BRH (1.04 vs 0.14/100 inpatients; p <0.0001). The nosocomial MRSA incidence-density was higher in DE-BRH than in NL-BRH (0.09 vs 0.03/1,000 patient days; p = 0.0002) and decreased significantly in DE-BRH (p = 0.0184) during the study. The rate of MRSA isolates from blood per 100,000 patient days was almost six times higher in DE-BRH than in NL-BRH (1.55 vs 0.26; p = 0.0041). The patients had longer hospital stays in DE-BRH than in NL-BRH (6.8 vs 4.9; p <0.0001). DE-BRH catchment area inhabitants appeared to be more frequently hospitalised than their Dutch counterparts. Conclusions: Ongoing IPC efforts allowed MRSA reduction in DE-BRH. Besides IPC, other local factors, including healthcare systems, could influence MRSA epidemiology.