Electronic cigarette use has raised concern worldwide regarding potential health risks and its position in tobacco cessation strategies. As part of any toxicity assessment, the chemical characterization of e-liquids and their related vapors are among fundamental data to be determined. Considering the lack of available reference methods, we developed and validated several analytical procedures in order to conduct a multicomponent analysis of six e-liquid refills and their resultant vapor emissions (generated by a smoking machine), and compared them with tobacco smoke. We combined several techniques including gas-chromatography, high and ultra-performance liquid chromatography and inductively coupled plasma with mass spectrometry or ultraviolet and flame ionization detection in order to identify the main e-liquid constituents (propylene glycol, glycerol and nicotine), as well as multiple potentially harmful components (trace elements, polycyclic aromatic hydrocarbons (PAHs), pesticides and carbonyl compounds). Regarding propylene glycol, glycerol and nicotine concentrations, the six tested e-liquids comply with the advertised composition and contain only traces of pollutants. Noticeable lower concentrations of trace elements (≤3.4 pg/mL puff), pesticides (<LOQ), PAHs (≤4.1 pg/mL puff) and carbonyls (≤2.11 ng/mL puff) were measured in e-vapors compared to those in cigarette smoke (up to 45.0 pg/mL puff, 8.7 pg/mL puff, 560.8 pg/mL puffand 1540 ng/mL puff, respectively). Although an accurate characterization of electronic cigarette emissions requires further analytical optimizations, our results have shown that vaping exposes the user to lesser amounts of selected toxic components of concern found in some representative French e-cigarette products than does smoking typical conventional cigarettes.