Health risks of fine particle air pollution (PM 2.5 ) are an important public health concern that has the potential to be mitigated in part by interventions such as air cleaning devices that reduce personal exposure to ambient PM 2.5 . To characterize exposure to ambient PM 2.5 indoors as a function of residential air cleaners, a multi-zone indoor air quality model was used to integrate spatially resolved data on housing, meteorology, and ambient PM 2.5 , with performance testing of residential air cleaners to estimate short-term and annual average PM 2.5 of outdoor origin inside residences of three metropolitan areas. The associated public health impacts of reduced ambient PM 2.5 exposure were estimated using a standard health impact assessment methodology. Estimated indoor levels of ambient PM 2.5 varied substantially among ventilation and air cleaning configurations. The median 24-h average indooroutdoor ratio of ambient PM 2.5 was 0.57 for homes with natural ventilation, 0.35 for homes with central air conditioning (AC) with conventional filtration, and 0.1 for homes with central AC with high efficiency in-duct air cleaner. Median modeled 24-h average indoor concentrations of PM 2.5 of outdoor origin for those three configurations were 8.4, 5.3, and 1.5 mg/m 3 , respectively. The potential public health benefits of reduced exposure to ambient PM 2.5 afforded by air cleaning systems were substantial. If the entire population of single-family homes with central AC in the modeling domain converted from conventional filtration to high-efficiency in-duct air cleaning, the change in ambient PM 2.5 exposure is estimated to result in an annual reduction of 700 premature deaths, 940 hospital and emergency room visits, and 130,000 asthma attacks in these metropolitan areas. In addition to controlling emissions from sources, high-efficiency whole-house air cleaner are expected to reduce exposure to particles of outdoor origin and are projected to be an effective means of managing public health impacts of ambient particle pollution.