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The objectives of this clinical study were to demonstrate a reduction in exposure to selected harmful and potentially harmful constituents (HPHCs), and to assess product use behavior, in Japanese healthy adult smokers who switched to a novel tobacco vapor product (NTV). 60 smokers were randomly assigned for 5 days to either (a) a group who switched to an NTV (n=20), (b) a group who continued to smoke their own brand of conventional cigarettes (CC, n=20) or (c) a smoking abstinence group (SA, n=20). Fifteen biomarkers of exposure (BoEs) to 14 HPHCs and pyrene were measured at baseline, day 3 and 5. Product use behavior was assessed by measuring product consumption, nicotine uptake and puffing topography. During investigations, increases were observed in product consumption and total puff volume in NTV group subjects as compared to baseline. Additionally, nicotine uptake in the NTV group was approximately half that observed in the CC group. BoE values were significantly reduced in the NTV group as compared to those in the CC group. Significantly, the magnitude of the reduction in exposure to HPHCs observed in the NTV group (49–94%) was close to that observed for the SA group (39–95%).A 5-day clinical study in smokers switching to a novel tobacco vapor product (NTV).The biomarkers of exposure (BoEs) were significantly reduced when switching to NTV.The changing in product use consumption when switching to the NTV were observed.The reductions in BoEs following switching to the NTV approached those following smoking abstinence.