ABSTRACT: INTRODUCTION:Many American Indian communities have a high prevalence of smoking and e-cigarette use, but factors associated with their dual use are rarely studied. METHODS:In 2016, a total of 375 American Indian adults who smoke completed paper surveys regarding cigarette and e-cigarette use and provided saliva for cotinine levels. In 2018, cross-sectional analyses were performed, comparing dual users (12%), defined as using e-cigarettes on some or every day for the past 30 days, with never users of e-cigarettes (37%). RESULTS:Compared with never users, dual users were younger, more often reported history of depression (56% and 29%, respectively; p<0.01) and family history of smoking-related disease (77% and 59%, respectively; p<0.05), had lower harm perceptions of e-cigarettes (27% and 47%, respectively; p<0.01) or vapor (14% and 35%, respectively; p<0.01), and more often perceived e-cigarettes as cessation aids (75% and 16%, respectively; p<0.01) and as less harmful than cigarettes (70% and 17%, respectively; p<0.01). Dual users were less often uncertain/unknowing about e-cigarette benefits or harms (p<0.01) and more often reported likelihood to quit smoking (49% and 24%, respectively; p<0.01) and prior attempt to quit smoking, ever (89% and 67%, respectively; p<0.01) or in the past year (55% and 32%, respectively; p=0.01). Cigarette consumption and cotinine levels did not differ between groups. Dual users more often tried other nicotine products (p<0.02) and more often lived with a vaping partner/spouse (45% and 6%, respectively; p<0.01). CONCLUSIONS:Dual users perceived e-cigarettes as less harmful than cigarettes and more as cessation aids than cigarette-only users did, but cigarette consumption did not differ between groups. Whether e-cigarettes will reduce smoking-related disparities among American Indian people remains undetermined.