Despite the growing popularity of heated tobacco products, there are few comprehensive studies on their environmental aerosols. Therefore, the impact of the Tobacco Heating System 2.2 (THS 2.2) on indoor air quality was evaluated on the basis of a comprehensive list of 31 airborne constituents along with targeted screening of the gas–vapor and particulate phases of the environmental aerosol. The assessments were conducted at three ventilation rates. Indoor use of THS 2.2 increased the levels of nicotine, acetaldehyde, glycerin, and (if mentholated products were used) menthol relative to background levels, with a corresponding increase in total volatile organic compounds (TVOC) values. Moreover, a temporary increase in ultrafine particles was observed when two or more tobacco sticks were used simultaneously or with a short time lapse between usages, but the concentrations returned to close to background levels almost immediately. This is because THS 2.2 generates an aerosol of liquid droplets, which evaporate quickly. Nicotine, acetaldehyde, glycerin, and TVOC levels were measured in the low μg/m3 range and were below the existing guideline limits. A comparison of airborne constituent levels during indoor THS 2.2 use with emissions from combustion products and common everyday activities revealed a substantially lower impact of THS 2.2 on the indoor environment.