Objectives: Initially marketed for smoking cessation, electronic cigarettes (e-cigarettes) are commonly regarded as safer than combustible cigarettes because they usually contain less nicotine and do not use combustion. However, few studies have examined the health effects of e-cigarettes. The objective of this study was to examine whether e-cigarette use had a differential effect on the prevalence of lung disease among current, former, and never tobacco users., Methods: We analyzed data from respondents aged ≥18 (n = 45 908) who responded to questions about e-cigarette use and lung disease in the 2016 Behavioral Risk Factor Surveillance System (BRFSS) survey. We calculated crude odd ratios (ORs) and ORs adjusted by 15 sociodemographic and health behavior factors: age, sex, race/ethnicity, annual household income, health insurance, personal physician, health status, body mass index, education, marital status, exercise, alcohol use, tobacco smoking, tobacco chewing, and metropolitan status., Results: We found a significant association between e-cigarette use and lung disease, which was significantly modified by tobacco use. Among never tobacco users, the adjusted odds of reporting lung disease were 4.36 (95% CI, 1.76-10.77) times higher among everyday e-cigarette users than among never e-cigarette users. Among current tobacco users, the adjusted odds of reporting lung disease were 1.47 (95% CI, 1.13-1.92) times higher among everyday e-cigarette users than among never e-cigarette users., Conclusions: People who have never smoked combustible cigarettes should refrain from starting e-cigarettes, because e-cigarettes carry a significant risk of lung disease independent of tobacco smoking. Additional prospective research into the harmful effects of e-cigarettes would help to further elucidate this link.