Background: Indoor air pollutants (IAPs) cause multiple health impacts. Prioritizing mitigation options that differentially impact individual pollutants and comparing IAPs to other environmental health hazards requires a common metric of harm. Objectives: The objective was to demonstrate a methodology to quantify and compare health impacts from IAPs. The methodology is needed to assess population health impacts of large-scale initiatives – including energy efficiency upgrades and ventilation standards – that affect indoor air quality (IAQ). Methods: Available disease incidence and disease impact models for specific pollutant-disease combinations were synthesized with data on measured concentrations to estimate the chronic heath impact, in Disability Adjusted Life Years (DALYs), due to inhalation of a subset of IAPs in U.S. residences. Model results were compared to independent estimates of DALYs lost due to disease. Results: PM2.5, acrolein, and formaldehyde accounted for the vast majority of DALY losses caused by IAPs considered in this analysis, with impacts on par or greater than estimates for secondhand tobacco smoke and radon. Confidence intervals of DALYs lost derived from epidemiology-based response functions are tighter than those derived from toxicology-based, inter-species extrapolations. Statistics on disease incidence in the US indicate that the upper-bound confidence interval for aggregate IAP harm is implausibly high. Conclusions: The demonstrated approach may be used to assess regional and national initiatives that impact IAQ at the population level. Cumulative health impacts from inhalation in U.S. residences of the IAPs assessed in this study are estimated at 400—1100 DALYs annually per 100,000 people.