This study evaluates the mortality-related benefits and costs of improvements in particle filtration in U.S. homes and commercial buildings based on models with empirical inputs. The models account for time spent in various environments as well as activity levels and associated breathing rates. The scenarios evaluated include improvements in filter efficiencies in both forced-air heating and cooling systems of homes and heating, ventilating, and air conditioning systems of workplaces as well as use of portable air cleaners in homes. The predicted reductions in mortality range from approximately 0.25 to 2.4 per 10 000 population. The largest reductions in mortality were from interventions with continuously operating portable air cleaners in homes because, given our scenarios, these portable air cleaners with HEPA filters most reduced particle exposures. For some interventions, predicted annual mortality-related economic benefits exceed $1000 per person. Economic benefits always exceed costs with benefit-to-cost ratios ranging from approximately 3.9 to 133. Restricting interventions to homes of the elderly further increases the mortality reductions per unit population and the benefit-to-cost ratios.