The policy of tobacco harm reduction – making less harmful products available to smokers who would otherwise continue smoking – has the potential to be beneficial to public health, provided that (1) risk reduction is established by sound science and (2) smokers find these products satisfying as alternatives to smoking cigarettes. Philip Morris International (PMI) has developed a portfolio of products with the potential to reduce the risk of cigarette smoking-related diseases. One such product, the Tobacco Heating System (THS) 2.2 heats tobacco without combustion, and the subsequent formation of harmful and potentially harmful constituents (HPHC) is greatly reduced compared with cigarette smoke. Assessment of the THS2.2 aerosol in vitro and in vivo reveals reduced toxicity and no new hazards. Additional mechanistic endpoints, measured as part of in vivo studies, confirmed reduced impact on smoking-related disease networks. Clinical studies have confirmed the reduced exposure to HPHCs in smokers switching to THS2.2 together with additional studies comparing the impact of switching on markers of disease risk. Additional elements of the integrated scientific assessment program include studies on risk perception and behavior for THS2.2 and post-market assessment studies.