Abstract Smoking during pregnancy is associated with serious and adverse outcomes for mothers and their infants. American Indian/Alaska Native (AI/AN) women have higher prevalence of smoking and poorer tobacco-related birth outcomes compared to other racial/ethnic populations. People who smoke are increasingly using electronic cigarettes (e-cigarettes) to quit smoking or reduce cigarette consumption. Since e-cigarettes have substantially lower levels of certain toxins compared to cigarettes, pregnant women may switch to these products in order to reduce the known risks associated with smoking. While e-cigarettes contain fewer toxins compared to cigarettes, these products still contain elements that may be harmful to the fetus, including nicotine. Yet, relatively few studies have evaluated e-cigarette use in pregnancy or the effects of e-cigarette use on birth outcomes. Further, no studies have assessed e-cigarette use among AI pregnant women, a population disproportionately affected by tobacco-related poorer birth outcomes. This observational cohort study will provide new insight into e-cigarette use and its association with birth outcomes, and harm versus benefit perceptions during pregnancy among 300 American Indian women receiving prenatal care at Cherokee Nation Health Services, using biochemical verification of toxicant exposure and smoking cessation, including cotinine, metabolite of nicotine, carbon monoxide, and survey data. We will pursue the following specific and exploratory aims: 1) Describe baseline prevalence of e-cigarette and other tobacco use, cotinine levels, and patterns of e-cigarette use among adult pregnant AI women in their first trimester; 2) Describe the baseline perceptions about the health risks related to tobacco and e-cigarette use during pregnancy and how they are associated with tobacco and e-cigarette use patterns; 3) Among the group of AI women in SA1 who used tobacco or e-cigarettes at baseline or within 3 months of pregnancy, explore the feasibility of reassessing smoking and e-cigarette use and cotinine exposures in the third trimester of pregnancy. We will explore the feasibility of recruiting and retaining pregnant AI women in a longitudinal study to assess product switching, changes in cigarettes smoked per day, change in nicotine exposure, and smoking cessation through pregnancy; 4) Assess the prevalence of low birth weight and preterm birth among infants born to AI women by e-cigarette and tobacco use status. We will explore the feasibility and acceptability of using medical records to assess birth outcomes overall and by baseline e-cigarette use and smoking status. E-cigarette use may potentially mitigate some of the health effects associated with cigarette use. Our project promises to illuminate patterns of e-cigarette use and its association with toxicant exposure in pregnancy and birth outcomes in a racial subpopulation disproportionately affected by tobacco-related diseases.