Electronic (e)-cigarettes have become immensely popular across the globe, but little is yet known about the impact of inhaling e-cigarette vapor on a daily basis. Conventional cigarettes are known to cause cardiopulmonary disease, with associated changes in heart rate, heart rate variability, blood pressure, ventricular function, airways resistance, airway reactivity and lung compliance. Many of these changes occur after decades of cigarette smoking, thus we may not know whether e-cigarettes will cause physiologic changes in humans for years to come. Therefore, we created a mouse model of e-cigarette vaping, and have exposed two different, genetically disparate, mouse strains to multiple types of e-cigarettes – including vape pens, Mods and JUULs – over 1-6 months to assess the impact of e-cigarette vapor inhalation on cardiopulmonary health. We have determined that inhalation of e-cigarette vapor on a daily basis is not benign. E-cigarette exposed mice develop cardiac fibrosis, a clear indication that myocardium is being damaged during e-cigarette use. Some mice develop airway reactivity and emphysema in a strain-specific manner, and this is also tied to specific types of e-cigarettes and the chemical composition of the e-cigarette vapor. There is much more work to be done to define the causal pathways behind e-cigarette effects on the mammalian system, which will hopefully lead to the development of safer devices.