An average reduction of more than 90 % in concentrations of harmful and potentially harmful constituents (HPHCs; among given lists) has been observed in the aerosols of commercial heated tobacco products (HTPs) and electronic cigarettes (ECs) relative to the corresponding concentrations in smoke from the 1R6F reference cigarette or commercial cigarettes. Recently, quantitative risk assessment has been performed to better characterize the impact of the decrease in individual HPHC levels in ECs and HTPs on health risk when compared with cigarettes. Different methodologies have been published based on incremental lifetime cancer risk or cancer potency values for estimating the cancer risk and based on hazard quotient or margin of exposure (MOE) for evaluating the non-cancer risk. Our analysis combined MOE and cancer potency values with the goal of estimating the cancer and non-cancer risks associated with exposure to HPHCs from a range of commercial HTPs and ECs in comparison with those from reference and commercial cigarettes on the basis of available compound specific toxicological threshold references from official regulatory agencies. HPHCs were measured in HTP aerosols from eight brands and in cigarette mainstream smoke from 273 brands. The cancer potency related to product emissions was then calculated and translated into mean lifetime cancer risk. MOEs were defined as the ratios of human inhalation exposure limits to the estimated human exposure levels for the considered HPHCs. Compared with cigarettes, the relative cancer risk from lifetime exposure was 0.039 for HTPs and 0.009 for ECs. Compared with cigarettes, the relative MOE was 55.45 for HTPs and 107.57 for ECs. HTPs and ECs showed a large decrease in estimated cancer and non-cancer risks relative to the predicted cancer and non-cancer risks from cigarettes.