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Introduction: the determinants of electronic cigarette (e-cigarette) use are not well understood; we aimed to explore the associations between health and e-cigarette use in a cross-sectional analysis among a large population-based cohort. Methods: the study population included 18,300 participants of the Constances cohort who were current users of e-cigarette and current or ex-smokers of tobacco, as assessed by a questionnaire. Logistic regressions provided odds ratios of e-cigarette use stratified on smoking status, adjusted for sociodemographic, health behavior, and health status variables (including respiratory and cardiovascular variables, and general health perception). Results: 17.4 and 4.0 % of current and ex-smokers used e-cigarette, respectively. In both smokers and ex-smokers, age was negatively associated with e-cigarette use, while increasing cumulative tobacco consumption and reported respiratory health were risk factors. For smokers, depression, a poor self-rated health, and being on a diet were positively associated with e-cigarette use; metabolic syndrome was negatively associated with e-cigarette use only when not on a diet. For ex-smokers, having a cardiovascular history and a longer time elapsed since tobacco cessation were negatively associated with e-cigarette use. Conclusions: our findings suggest that e-cigarette is used as an attempt for smokers to quit or reduce tobacco smoking, and for ex-smokers to avoid relapsing. E-cigarette use among these subjects has to be medically supervised, especially since e-cigarette seems a good marker of a willingness to quit or reduce smoking for health reasons.