Electronic cigarette (EC) use for smoking cessation and harm reduction has divided opinions in scientific and smoking cessation communities. Opinions are diverse from EC being the answer to the global tobacco epidemic to EC being a major public health concern both in their own right and as a gateway into smoking. Many of the concerns around EC use focus upon addiction and potential health effects from long-term exposures to EC aerosol especially upon the respiratory system. The smokefreebrain study is a H2020-funded project which includes an examination of EC to investigate some key questions with respect to toxicity including toxicant exposures and formation of carcinogens, effects upon markers of inflammation and effects upon enzymes involved in the bioactivation of environmental procarcinogens. EC aerosol was generated using an Innokin Endura T18E vape pen through a commercially available EC aerosol generating system (e-aerosols, NY) employing the CORESTA EC puff profile (55 ml puff volume, 3 s puff duration, 30 s puff interval, and a square wave puff profile. In vitro studies employed human pulmonary hBEC-3KT cells exposed to aerosol generated from differently flavoured e-liquids either with or without nicotine in an air-liquid interface system. Endpoints focussed upon cell viability, and markers of inflammation and oxidative stress. Male AJ mice (n=9) were exposed to aerosol from tobacco-flavoured e-liquid, (0, 6 mg/ml and 18 mg/ml nicotine; 50:50 PG:VG) or air-only controls for 14 consecutive days by the nose only route. Primary endpoints in this hazard identification study included whole body and organ weights, carcinogen biomarker studies, changes to nicotinic acetylcholinesterase receptors in brain, and targeted metabolomics. Finally, a longitudinal study of heavy smokers (n=55) switching to EC only use was conducted with the aim of monitoring toxicant exposures, including nicotine, through urinary and salivary biomarkers together with psychometric measures (nicotine dependence, nicotine withdrawal, anxiety, urges to smoke/vape etc). In addition, a subset of participants (n=13) had their brain electrical activity measured using electroencephalography, before and 3 weeks after the transition to EC-only use. Finally, participants that completed the 28-day intervention (n=31) were followed up at 6 and 12 months and smoking status determined. Here we will present the findings of these studies and discuss the possible consequences for human health.