Methicillin-resistant Staphylococcus aureus (MRSA) has become less common in Germany in recent years. In this paper, we report data from the MRSA module of the Hospital Infection Surveillance System (Krankenhaus-Infektionen- Surveillance-System, KISS) for the years 2006-2021. We also describe the association of MRSA rates with the frequency of patient screening for MRSA and discuss the findings. Participation in the MRSA KISS module is voluntary. Once a year, the participating hospitals submit structural data, information on cases in which MRSA was detected (both colonizations and infections; both detected on admission and nosocomially acquired), and the number of nasal swabs taken for the detection of MRSA to the German National Reference Center for the Surveillance of Nosocomial Infections. Statistical analyses were performed with R software. The number of hospitals participating in the MRSA module rose from 110 in 2006 to 525 in 2021. From 2006 onward, the overall MRSA prevalence in German hospitals increased, reaching a maximum of 1.04 cases per 100 patients in 2012. The prevalence on admission fell by 44% from 0.96 in 2016 to 0.54 in 2021. The incidence density of nosocomial MRSA fell by an average of 12% per year, from 0.27 per 1000 patient-days in 2006 to 0.06 in 2021, while MRSA screening frequency increased sevenfold by 2021. The nosocomial incidence density was stable, independently of the screening frequency. MRSA rates in German hospitals fell markedly from 2006 to 2021, reflecting a general trend. The incidence density was no higher in hospitals with a low or moderate screening frequency than in those with a high one. Thus, a targeted, riskadapted MRSA screening strategy on hospital admission can be recommended.