Our study examined what demographic and health factors were associated with motivations for e-cigarette use in those with asthma and COPD. The analysis included participants ≥ 18 years old in Wave 5 of the Population Assessment of Tobacco and Health who reported e-cigarette use and had asthma or COPD. We used multivariable logistic regression models, adjusted for survey weights, to examine the associations of potential reasons for e-cigarette use, including affordability and attempts to minimize or quit cigarette smoking. Seven hundred twenty-five participants (weighted n = 2,588,403) met the inclusion criteria. Factors associated with using e-cigarettes to help reduce cigarette use included being > 45 years old (odds ratio 1.9, 95% confidence interval 1.1–3.2) and having experienced wheezing in the past year (2.1, 1.3–3.4). Experiencing wheezing was also the only factor associated with using e-cigarettes to help quit smoking (2.6, 1.5–4.5). Being Hispanic and being moderately to very worried about the health impacts of any tobacco product usage, which includes electronic products, conferred a lower likelihood of using e-cigarettes to cut down on cigarettes (0.5, 0.3–0.98; 0.4, 0.3–0.8). Those who identified as male or being moderately to very worried about the health impacts of their tobacco product usage were significantly less likely to have initiated e-cigarettes for smoking cessation (0.6, 0.4–0.9; 0.3, 0.2–0.5). Factors associated with the uptake of e-cigarettes as a smoking cessation tool include age, gender, and ethnicity. Wheezing, as a symptom of respiratory illness, appears to have the strongest association with e-cigarette usage as a form of smoking cessation. At the same time, concern about the health impacts of tobacco products is the strongest negative predictor.