According to the 2012 Food and Drug Administration (FDA)’s Modified Risk Tobacco Product (MRTP) draft guidance, there is an inherent difficulty in making premarket assessments of the effect of introducing an MRTP on the population as a whole. FDA therefore encourages the development and application of innovative analytical methods to make preliminary estimates of the potential effects including modeling. Philip Morris International is developing a Population Health Impact Model to assess the effect that the introduction of a MRTP would have on the population. The modeling approach uses available smoking prevalence and disease-specific mortality data as well as relative risk (RR) estimates for the most common smoking related diseases from epidemiological studies. Calculations rely on generally acknowledged methods and it is a goal to reduce the number of necessary assumptions to a minimum. The model will consist of two major components, the Prevalence (P) and Epidemiological (E) Risk Component. The P-Component uses a state-transition Monte Carlo microsimulation model to estimate changes in the distribution of smoking habits (combustible cigarette (CC) and/or MRTP) occurring in a hypothetical population of a given size over a defined period, separately for a scenario where the MRTP is introduced and a scenario where it is not. The E-Component uses estimates of the RRs of smoking-related diseases for current smokers compared to never smokers and for former smokers by time quit to estimate the number of smoking-attributable deaths. The MRTP-related risk reduction quantification will be based on a comprehensive risk assessment integrating evidence on non-clinical and clinical research. Using an estimate of the exposure from the MRTP relative to CCs and smoking cessation, the model compares smoking-attributable deaths under each scenario to derive the estimated reduction in smoking-attributable mortality associated with the introduction of a MRTP.