The analysis of aerosol and gas phase volatile organic compounds (VOC) emitted by vapor products has relied on a variety of standardized but time - consuming off-line technologies. Conventional methods typically involve the capture of aerosol from multiple sequential puffs (~50) on a filter pad, or in an impinger solution, followed by extraction and derivatization. These procedures are resource intensive and have low time-resolution, prohibiting puff-by-puff analysis, and may lead to sample alteration due to evaporation, water uptake, or chemical reactions on the filter. In this study, we present a novel methodology which combines a high-resolution PTR-MS with an improved aerosol dilution system and an actuating device to trigger aerosol production from the vapor product and direct it to the dilution system. We employed this methodology to analyze and quantify harmful or potentially harmful constituents (HPHCs), such as acrolein, acetaldehyde, acrylonitrile, crotonaldehyde, and nicotine-n-oxide, in aerosol emitted from vapor products on a puff-by-puff basis in real-time. Concentrations of several compounds were determined puff-by-puff and validated with results obtained from a contract research laboratory using ISO 17025 accredited methods. The chemical puff profiles of different devices (e.g. temperature-regulated, unregulated, and ciga-likes) are presented. The real-time data demonstrates that harmful compounds were not detected for temperature regulated devices for the life of the pod, while in contrast, devices without temperature regulation exhibited significant increase of harmful compounds such as carbonyls and oxides at the end of liquid. We demonstrate that PTR-MS may be used as an alternative to off-line methods for simultaneous quantification and characterization of most HPHCs found in aerosol as well as VOCs, puff-by-puff, and even intra-puff to enable immediate assessment of new nicotine-containing formulations, changes in device design, and validation of product designs.