Exposures to vehicle-emitted PM2.5, black carbon (BC), and ultrafine particles (UFPs), have been associated with adverse health effects. As a potential strategy to mitigate in-cabin exposure, the authors developed a novel high efficiency cabin air (HECA) filter for passenger vehicles and an on-board HECA filtration system for school buses. Their performance was evaluated in twelve passenger vehicles and six school buses, respectively. UFP number concentration and size distribution as well as BC and PM2.5 levels were concurrently monitored inside and outside of each vehicle under three driving conditions: stationary, on local roadways, and on freeways. For passenger vehicles, data were collected with no filter, the in-use original equipment manufacturer (OEM) filter, and two prototypes of HECA filters (i.e., HECA A and B filters). For school buses, data were collected with and without operating the filtration system equipped with HECA B filters. For passenger vehicles, the HECA B filters offered in-cabin concentration reductions of 90 ± 8% for UFPs on average across all driving conditions, much higher than the OEM filters (50 ± 11% on average). Similarly, the HECA B filters offered an 81 ± 15% reduction for BC and 66 ± 28% for PM2.5 across all driving conditions. In comparison, across all driving conditions, in-use OEM filters only provided 31 ± 17% and 29 ± 20% reduction for BC and PM2.5, respectively. For school buses, across all driving conditions, in-cabin UFP and BC levels were reduced by 88 ± 6% and 84 ± 5% on average, respectively, when the on-board HECA filtration system was operating. The HECA system achieved 55 ± 22% reductions on average for PM2.5 and successfully kept its levels below 12 μg/m3.