Background: The efficacy of the high-efficiency particle arresting (HEPA) air cleaner and its related health benefits have gotten some attention, yet the number of studies on this topic is still modest. Recently, a commercially available “auto-mode” air cleaner has emerged on the market that adjusts the operating fan speed automatically depending on its built-in particulate matter (PM) sensor, which may improve real-world effectiveness since it doesn't rely on the user to adjust the air cleaner when they perceive the air is polluted. Objectives: We sought to assess the impact of auto-mode filtration on indoor PM exposure and cardiovascular health among healthy, non-smoking adults in an urban United States location. Methods: The study approach was a randomized, crossover 3-way air filtration intervention pilot study in the urban Seattle area from February 1 to March 29, 2019. Six non-smoking, healthy young adults were enrolled in the study, provided an air cleaner, and exposed to each of the three following intervention scenarios for 1 week (order of interventions randomized), with each one separated by a washout period of at least two weeks in duration: (1) a control period consisting of a sham filter installed in the air cleaner, (2) an intervention consisting of the air cleaner set to auto-mode filtration, and (3) an intervention in which participants were allowed to adjust the settings of the air cleaner. In all cases, the air cleaner was used in the participant’s living room. Participants were asked to take two blood pressure measurements daily at 8 am and 8 pm. Indoor area PM2.5 monitoring was conducted in both the kitchen and the living room of each household using a continuous particle counter. Results: The indoor mean PM2.5 levels measured in the living room and the kitchen were significantly reduced by 5.05 Âµg/m3 (95% CI [-6.19, -3.91]; p<0.001) and 6.60 Âµg/m3 (95% CI [-7.86, -5.34]; p<0.001) , respectively under the auto-mode filtration compared to the sham-mode filtration; whereas under the adjustable-mode filtration, the indoor PM2.5 level was significantly decreased by 3.43 Âµg/m3 (95% CI [-4.57, -2.28]; p<0.001) and 5.01 Âµg/m3 (95% CI [-6.27, -3.76]; p<0.001) in the living room and kitchen, respectively, compared to sham-mode filtration. Auto-mode filtration significantly reduced the indoor mean PM2.5 levels in the living room and the kitchen by 1.63 Âµg/m3 (95% CI [-2.76, -0.48]; p=0.01) and 1.59 Âµg/m3 (95% CI [-2.84, -0.34]; p=0.04), respectively, compared to adjustable-mode filtration. 12-hour personal exposure, which accounted for time-activity patterns and exposures away from home, was reduced by 5.45 Âµg/m3 (95% CI [-9.51,-1.39]; p=0.01) under the auto-mode filtration and 4.26 Âµg/m3 (95% CI [-8.37, -0.14]; p<0.05) under the adjustable-mode filtration, compared to sham-mode. Auto-mode reduced the 12-hour personal exposure by 1.19 Âµg/m3 (95% CI [-6.11, 3.73]; p=0.8), compared to adjustable-mode filtration. A near statistically significant decrease in morning systolic blood pressure of 6.1 mm-Hg (95% CI [-12.5, 0.3]; p=0.06) was found under the auto-mode filtration compared to sham-mode. Conclusions: Results of this study indicated that using HEPA auto-mode filtration resulted in higher reductions in indoor PM2.5 level and personal PM2.5 exposures. Using an auto-mode air cleaner may lead to real-world effectiveness for reducing indoor PM2.5 exposure. The findings on morning blood pressure are suggestive that auto-mode filtration may improve cardiovascular health.