Preventing adolescents from using e-cigarettes is crucial given that e-cigarette use can lead to conventional cigarette smoking. In order to inform prevention efforts, the present study examined the role of susceptibility measures as well as psychosocial, behavioral, and environmental factors in prospectively predicting ever use of electronic cigarettes among adolescents. We analyzed Wave 1 and Wave 2 of the Population Assessment of Tobacco and Health (PATH), nationally representative longitudinal panel datasets. Nicotine naïve adolescents, ages 12-17 at baseline (N = 7933) were included in the study sample. Multivariable logistic regression was conducted to examine the determinants of adolescents' ever use of e-cigarettes. Overall, 12.3% (n = 983) of adolescents who were naïve to nicotine products at Wave 1 became ever users of e-cigarettes at Wave 2. Susceptibility to e-cigarette use at Wave 1 was a significant predictor of ever use at Wave 2 (adjusted odds ratio = 2.27; 95% CI = 1.92, 2.68). Adolescents who were not susceptible to e-cigarette use at Wave 1 but became ever users at Wave 2 were more likely to show a higher level of alcohol use, marijuana use, other substance use, have modified family, be exposed to secondhand tobacco smoke, and have a higher level of psychological problems. The specificity of susceptibility measure was 73.2% (5080/6936) and sensitivity was 57.3% (563/983). The findings of the present study appear to support the predictive validity of the susceptibility to e-cigarette use measure as a significant predictor of future e-cigarette use.