Objectives Electronic cigarette (e-cigarette) use has increased steadily in the United States, but little research has examined its prevalence in states comprising Appalachia, a rural region known for high rates of tobacco use. This study assessed lifetime and current e-cigarette use among adults by sociodemographic characteristics, geographic region, and cigarette smoking in Kentucky, with a focus on the Appalachian region. Methods We used data from the 2016-2017 Behavioral Risk Factor Surveillance System (BRFSS) surveys to calculate the prevalence of lifetime and current e-cigarette use, and we used weighted multivariable logistic regression analyses to examine the relative influence of other factors. Results Among adults in Kentucky, 5.8% (95% CI, 5.2%-6.4%) were current e-cigarette users and 27.0% (95% CI, 25.9%-28.0%) were lifetime users, compared with state medians of 4.6% (95% CI, 4.0%-5.1%) and 21.4% (95% CI, 19.4%-23.5%) for the United States. Multivariable regression models showed similar patterns for all regions: higher prevalence odds of current e-cigarette use among adults aged 18-24, current conventional smokers, and adults unable to work. Generally, Appalachian residents of Kentucky did not have significantly higher rates of lifetime or current e-cigarette use as compared with other non-Appalachian residents of Kentucky. Hispanic residents of Appalachian Kentucky, however, had higher rates of e-cigarette use than Hispanic residents of other regions of Kentucky. Conclusions Rates of e-cigarette use were higher in Kentucky than in the United States but were not further elevated in Kentucky’s Appalachian region. High rates of e-cigarette use among Hispanic residents of Appalachia indicate a need to focus future interventions in the region.