Background Dutch policy makers needed a knowledge base for prioritising control of different indoor air pollutants. Several burden of disease (BoD) estimates were available, but it was not known if they could be applied to The Netherlands. Objectives To quantify the BoD related to indoor air in The Netherlands, and to compare the outcomes with a previous study (EnVIE), which used a different BoD methodology. Results The largest BoD was attributable to environmental tobacco smoke. The next most important indoor air pollutants were radon and thoron from soils and building materials, followed by dampness and carbon monoxide (CO). Formaldehyde exposure did not contribute to the total BoD, according to our estimates. The EnVIE estimate was three times higher, and the most important indoor air pollutants by BoD were combustion products from outdoor sources, bioaerosols due to dampness and by outdoor sources, volatile organic compounds, radon from soils, pathogens and CO. The differences in estimates were primarily caused by the different selection or definition of substances in indoor air, rather than the differing BoD methodology. Conclusions Indoor air exposure is associated with a considerable BoD in The Netherlands; approximately 1500 healthy life years per 1 million inhabitants are lost due to 1 year of exposure. The results from the different BoD studies examined here are difficult to compare—even the relative order of most important pollutants depends on choices and assumptions in the assessment. A careful evaluation of BoD estimates is required before they can be used in policy making.