Background: Despite rapid growth in the use of electronic cigarettes (ECIGs) in the U.S., few studies have examined the national prevalence of ECIG use among adults with disabilities. Objective: To assess the national prevalence of and risk factors for ECIG use among working-age (18–64 years) adults with and without disabilities. Methods: This observational study relied on a sample of 560,858 working-age adults from the 2017–2018 Behavioral Risk Factor and Surveillance System (BRFSS). We conducted descriptive analyses to estimate the prevalence of ECIG use and multivariate logistic regression models to examine factors associated with ECIG use among adults with and without disabilities. Results: ECIG use was more prevalent among adults with a cognitive disability (12.0%), an independent living disability (11.0%), or two or more disabilities (9.2%), compared to adults without disabilities (4.8%). In the multivariate analysis, adults with a cognitive disability (OR = 1.45; p < .001), ambulatory disability (OR = 1.23; p < .05), and those with two or more disabilities (OR = 1.49; p < .001) had an increased likelihood of ECIG use compared to those without disabilities. Current smokers had greater odds of using ECIGs compared to never smokers (OR = 8.53, p < .001). Conclusions: Adults with cognitive disabilities and independent living disabilities had more than twice the prevalence of ECIG use compared to adults without disabilities. Future studies should monitor the rising prevalence and risk factors for ECIG use as well as examine longitudinal associations between using ECIGs, dual use with cigarette smoking, and health outcomes among adults with disabilities.