We recently developed a novel tobacco vapor product (NTV) that comprises a battery, a cartridge with a heater and nicotine-free liquid, and a tobacco capsule filled with tobacco blend. Vapor containing nicotine and flavor is produced by aerosol from the cartridge that passes through the capsule during inhalation. The results of the chemical analysis of vapor showed that most of the measured selected cigarette smoke constituents were below quantifiable levels, suggesting that switching to NTV reduces the exposure to these constituents. The present study aimed to investigate the level of exposure to selected harmful and potentially harmful constituents (HPHCs) of cigarette smoke in adult smokers who switched to NTV compared with those who continued to smoke their own brands of commercial cigarettes (CC). We also assessed the level of exposure in adult smokers who abstained from smoking (SA) as a benchmark of exposure reduction. Sixty healthy Japanese smokers were randomized to the NTV, CC, and SA groups for five days under confined conditions, and 15 biomarkers of exposure (BoEs) to 14 HPHCs and pyrene were measured at baseline, day three, and day five (UMIN000025777). The levels of all BoEs were significantly reduced in the NTV group compared with the CC group. Of significance, the magnitude of the reduction in exposure to HPHCs observed in the NTV group (49 %-94 %) was close to that observed in the SA group (39 %-95 %). This result indicates that the level of exposure to smoke constituents can be reduced in smokers by switching to NTV from cigarette smoking compared with smokers who continued smoking CC, and the level of exposure can be reduced to the level observed when smokers abstained from smoking.