To investigate use of electronic nicotine delivery systems (ENDS) among priority populations. Using 2016 through 2017 US nationally representative surveys (n = 11 688), we examined ENDS use by sociodemographic variables (age, education, poverty status, insurance, employment, race/ethnicity, sexual orientation) and combustible tobacco use. Among individuals who currently use noncigarette combustible tobacco, those from certain backgrounds (young adults, those living below the poverty level, those less educated, sexual minorities, Blacks, Hispanics, and those without health insurance) were more likely to use ENDS. Among current cigarette smokers, those who were younger, living at or above poverty (ever use), with higher education (current use), sexual minority, and non-Black were more likely to use ENDS. Associations between sociodemographic variables and ENDS use varied depending on combustible tobacco use status, highlighting the need to consider multiple types of tobacco products to understand ENDS use among priority populations. The impact on tobacco disparities will ultimately depend on whether ENDS are used to transition completely away from combustible tobacco products and how this may differ across priority populations who use diverse tobacco products.