Outdoor traffic‐related airborne particles can infiltrate a building and adversely affect the indoor air quality. Limited information is available on the effectiveness of high efficiency particulate air (HEPA) filtration of traffic‐related particles. Here, we investigated the effectiveness of portable HEPA air cleaners in reducing indoor concentrations of traffic‐related and other aerosols, including black carbon (BC), PM2.5, ultraviolet absorbing particulate matter (UVPM) (a marker of tobacco smoke), and fungal spores. This intervention study consisted of a placebo‐controlled cross‐over design, in which a HEPA cleaner and a placebo “dummy” were placed in homes for 4‐weeks each, with 48‐hour air sampling conducted prior to and during the end of each treatment period. The concentrations measured for BC, PM2.5, UVPM, and fungal spores were significantly reduced following HEPA filtration, but not following the dummy period. The indoor fraction of BC/PM2.5 was significantly reduced due to the HEPA cleaner, indicating that black carbon was particularly impacted by HEPA filtration. This study demonstrates that HEPA air purification can result in a significant reduction of traffic‐related and other aerosols in diverse residential settings.