E-cigs are often used in order to reduce or quit smoking. American Indians (AIs) have a high prevalence of cigarette use but their use of e-cigs has never been examined in relation to smoking quit attempts or exposures to tobacco constituents. Baseline survey and biomarker data were collected for 375 adult AI smokers at a Cherokee Nation healthcare facility in 2016 for an observational cohort study. We conducted multivariate regression analyses on the data to assess associations between e-cig use and previous quit attempts, likelihood to quit smoking, confidence to quit smoking, cigarette packs smoked per day, salivary cotinine levels, and exhaled carbon monoxide (CO). In adjusted analyses, current and past e-cig users were more likely than never users to report any lifetime quit attempt. Current and past users were also more likely to report a likelihood to quit smoking. E-cig use was not significantly associated with confidence to quit smoking, cigarette packs smoked per day, cotinine levels, or exhaled CO levels. While e-cig use may not be associated with these tobacco-related behaviors and exposures among current smokers, such use may indicate a higher level of readiness to quit smoking. Inquiring about e-cig use among AIs smokers may provide an opportunity for public health professionals to promote evidence-based cessation programs. Longitudinal studies are needed to determine if dual users will have more success in reducing smoking than those who do not use e-cigs.Discuss e-cig use among American Indians, who smoke, living in Oklahoma.Discuss the association between e-cig use and tobacco-related behaviors and exposures among American Indians, who smoke.Discuss preliminary data from follow-up data collection of the cohort study.