Summary There is renewed interest in the hospital environment as a potentially important factor for cross-infection with methicillin-resistant Staphylococcus aureus (MRSA) and other nosocomial pathogens. The aim of this study was to evaluate the effectiveness of a portable high-efficiency particulate air (HEPA)-filtration unit (IQAir Cleanroom H13, Incen AG, Gold-ach, Switzerland) at reducing MRSA environmental surface contamination within a clinical setting. The MRSA contamination rate on horizontal surfaces was assessed with agar settle plates in ward side-rooms of three patients who were heavy MRSA dispersers. Contamination rates were measured at different air filtration rates (60-235 m3/h) and compared with no air filtration using Poisson regression. Without air filtration, between 80% and 100% of settle plates were positive for MRSA, with the mean number of MRSA colony-forming units (cfu)/10-h exposure/plate ranging from 4.1 to 27.7. Air filtration at a rate of 140 m3/h (one patient) and 235 m3/h (two patients), resulted in a highly significant decrease in contamination rates compared with no air filtration (adjusted rate ratios 0.037, 0.099 and 0.248, respectively; P< 0.001 for each). A strong association was demonstrated between the rate of air filtration and the mean number of MRSA cfu/10-h exposure/plate (P for trend < 0.001). In conclusion, this portable HEPA-filtration unit can significantly reduce MRSA environmental contamination within patient isolation rooms, and this may prove to be a useful addition to existing MRSA infection control measures.