Introduction - There is no evidence in the literature relating to the evolution of e-cigarette use among cannabis users and multi-users (of alcohol, tobacco or cannabis). Objective - To describe the evolution over 12 months of e-cigarette use in cannabis users and multi-users. Methods - A prospective observational cohort study in general practice, between 2015 and 2016. Results - A total of 4.8% of monitored cannabis users remained or became current users of e-cigarettes by the end of the monitoring period versus 4.5% among non-users of cannabis, with no statistically significant difference. A total of 5.1% of monitored multi-users remained or became current users of e-cigarettes by the end of the monitoring period versus 2.4% among the non-multi-users, with no statistically significant difference. Cannabis users and multi-users reported more e-cigarette experimentation through curiosity and following someone's suggestion, compared to non-cannabis users or non multi-users. No statistically significant association was found between cannabis or multi-drug use and staying or becoming a current e-cigarette user over 12 months. Conclusion - Cannabis users and multi-users would tend to experiment with e-cigarettes more than other patients but this use would not be sustained.