Although electronic cigarettes (ECs) are a much less harmful alternative to tobacco cigarettes, there is concern as to whether long-term ECs use may cause risks to human health. We report health outcomes (blood pressure, heart rate, body weight, lung function, respiratory symptoms, exhaled breath nitric oxide [eNO], exhaled carbon monoxide [eCO], and high-resolution computed tomography [HRCT] of the lungs) from a prospective 3.5-year observational study of a cohort of nine daily EC users (mean age 29.7 (±6.1) years) who have never smoked and a reference group of twelve never smokers. No significant changes could be detected over the observation period from baseline in the EC users or between EC users and control subjects in any of the health outcomes investigated. Moreover, no pathological findings could be identified on HRCT of the lungs and no respiratory symptoms were consistently reported in the EC user group. Although it cannot be excluded that some harm may occur at later stages, this study did not demonstrate any health concerns associated with long-term use of EC in relatively young users who did not also smoke tobacco.