Background: Smoking prevalence and mortality is 5 times higher for the chronically homeless versus general population. Unfortunately, traditional smoking cessation treatment does not optimally engage this population. In a preliminary study, smokers experiencing chronic homelessness suggested providers avoid giving advice to quit and instead use a more compassionate, nonjudgmental style to discuss a broader menu of patient-driven options, including safer nicotine use. Most had negative perceptions of smoking cessation medications; however, 76% expressed interest in a switchover to electronic nicotine delivery systems (ENDS). Methods: Using a community-based participatory research approach, we codeveloped harm-reduction treatment for smoking (HaRT-S) together with people with lived experience of chronic homelessness and smoking and a community-based agency that serves them. In HaRT-S, interventionists embody a compassionate, advocacy-oriented "heart-set" and deliver manualized components: a) participant-led tracking of smoking-related outcomes, b) elicitation of harm-reduction goals and progress made toward them, c) discussion of relative risks of nicotine delivery systems, and d) distribution and instructions on use of safer nicotine products. We then conducted a single-arm, 14-week pilot of HaRT-S (N = 44). Results: Participants rated procedures "totally acceptable/effective," which was reflected in 26% overrecruitment within a 4-month period and 70% retention at the 14-week follow-up. For each week in the study, participants experienced an 18% increase in odds of reporting 7-day, biochemically verified, point-prevalence abstinence. All participants reporting abstinence used ENDS. Participants evinced reductions in cigarette dependence (-45%), frequency (-29%), and intensity (-78%; ps < .05). Participants who used ENDS experienced an additional 44% reduction in smoking intensity and a 1.2-point reduction in dependence compared to participants who did not. Conclusions: Harm-reduction counseling plus ENDS shows promise for smokers experiencing chronic homelessness. Randomized controlled trials are needed to establish the efficacy of this approach in decreasing smoking-related harm and improving health-related quality of life for this marginalized and disproportionately affected population.

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