The overarching aims of this study are to (a) estimate and update knowledge on rates and predictors of awareness, perceived harmfulness, and ever use of e-cigarettes among U.S. adults and (b) to utilize that information to identify risk-factor profiles associated with ever use. Data were collected from the 2015 Health Information National Trends Survey (N=3,738). Logistic regression was used to explore relationships between sociodemographics (gender, age, race/ethnicity, sexual orientation, educational attainment, income, and census region), current use of other tobacco products (conventional cigarettes, cigars, and smokeless tobacco), ever use of alternative products (hookah, pipes, roll-your-own cigarettes, and snus) and e-cigarette awareness, perceived harm, and ever use. Classification and regression tree (CART) modeling was used to examine risk-factor profiles of e-cigarette ever use. Results showed that most respondents were aware of e-cigarettes (83.6%) and perceived them to be not at all or moderately harmful (54.7%). Prevalence of e-cigarette ever use was 22.4%. Current cigarette smoking and ever use of alternative tobacco products were powerful predictors of use. Other predictors of use of e-cigarettes were age, race/ethnicity, and educational attainment. Awareness and perceived harm were significant predictors among particular smoker subgroups. Fifteen risk profiles were identified across which prevalence of e-cigarette use varied from 6-94%. These results underscore the need to continue monitoring patterns of e-cigarette use. They also provide new knowledge regarding risk-profiles associated with striking differences in prevalence of e-cigarette use that have the potential to be helpful when considering the need for or impact of e-cigarette regulatory policies.