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Background: Smoke exposure from wildfires or residential wood burning for heat is a public health problem for many communities. Do-It-Yourself (DIY) portable air cleaners (PACs) are promoted as affordable alternatives to commercial PACs, but evidence of their effect on health outcomes is limited. Objective: Pilot test an evaluation of the effect of DIY PAC usage on self-reported symptoms, and investigate barriers and facilitators of PAC use, among members of a tribal community that routinely experiences elevated concentrations of fine particulate matter (PM2.5) from smoke. Methods: We conducted studies in Fall 2021 (“wildfire study”; N = 10) and Winter 2022 (“wood stove study”; N = 17). Each study included four sequential one-to-two-week phases: 1) initial, 2) DIY PAC usage ≥8 h/day, 3) commercial PAC usage ≥8 h/day, and 4) air sensor with visual display and optional PAC use. We continuously monitored PAC usage and indoor/outdoor PM2.5 concentrations in homes. Concluding each phase, we conducted phone surveys about participants’ symptoms, perceptions, and behaviors. We analyzed symptoms associated with PAC usage and conducted an analysis of indoor PM2.5 concentrations as a mediating pathway using mixed effects multivariate linear regression. We categorized perceptions related to PACs into barriers and facilitators of use. Results: No association was observed between PAC usage and symptoms, and the mediation analysis did not indicate that small observed trends were attributable to changes in indoor PM2.5 concentrations. Small sample sizes hindered the ability to draw conclusions regarding the presence or absence of causal associations. DIY PAC usage was low; loud operating noise was a barrier to use. Discussion: This research is novel in studying health effects of DIY PACs during wildfire and wood smoke exposures. Such research is needed to inform public health guidance. Recommendations for future studies on PAC use during smoke exposure include building flexibility of intervention timing into the study design.