Fine particulate air pollution (PM2.5) is a major environmental contributor to human burden of disease and therefore an important component of life cycle impact assessments. An accurate PM2.5 characterization factor, i.e., the impact per kilogram of PM2.5 emitted, is critical to estimating “cradle-to-grave” human health impacts of products and processes. We developed and assessed new characterization factors (disability-adjusted life years (DALY)/kg(PM2.5 emitted)), or the products of dose-response factors (deaths/kg(PM2.5 inhaled)), severity factors (DALY/death), and intake fractions (kg(PM2.5 inhaled)/kg(PM2.5 emitted)). In contrast to previous health burden estimates, we calculated age-specific concentration- and dose-response factors using baseline data, from 63 US metropolitan areas, consistent with the US study population used to derive the relative risk. We also calculated severity factors using 2010 Global Burden of Disease data. Multiplying the revised PM2.5 dose responses, severity factors, and intake fractions yielded new PM2.5 characterization factors that are higher than previous factors for primary PM2.5 but lower for secondary PM2.5 due to NOx. Multiplying the concentration-response and severity factors by 2005 ambient PM2.5 concentrations yielded an annual US burden of 2,000,000 DALY, slightly lower than previous US estimates. The annual US health burden estimated from PM emissions and characterization factors was 2.2 times higher.