Introduction and Objectives: Philip Morris International is currently developing potentially reduced risk products (RRPs) with the intention to reduce the risk of tobacco-related diseases. The challenge indeveloping RRPs is two fold, i.e., developing tobacco products that are shown to reduce risk and that are acceptable to smokers as substitutes for combustible cigarettes (CC). The candidate RRP, the Tobacco Heating System (THS)2.2, tested in this study is heated at significantly lower temperatures than required for CC. The study reported here is part of a global clinical program and the objective of the study was to evaluate the plasma pharmacokinetic (PK) profile of nicotine following single use of THS2.2 menthol and non-menthol as compared to menthol and non-menthol combustible cigarettes (CC) and nicotine replacement therapy (NRT), respectively. Subjective effects were evaluated to get first insight to which extent adult smokers would find THS2.2 an acceptable substitute for CC.