Active sub-slab depressurization (SSD) systems are an effective means of reducing indoor radon concentrations in residential buildings. However, energy is required to operate the system fan and to heat or cool the resulting increased building ventilation. We present regional and national estimates of the energy requirements, operating expenses and CO2 emissions associated with using SSD systems at saturation (i.e. in all US homes with radon concentrations above the EPA remediation guideline and either basement or slab-on-grade construction). The primary source of uncertainty in these estimates is the impact of the SSD system on house ventilation rate. Overall, individual SSD system operating expenses are highest in the Northeast and Midwest at about $99 y(-1), and lowest in the South and West at about $66 y(-1). The fan consumes, on average, about 40% of the end-use energy used to operate the SSD system and accounts for about 60% of the annual expense. At saturation, regional impacts are largest in the Midwest because this area has a large number of mitigable houses and a relatively high heating load. We estimate that operating SSD systems in US houses, where it is both appropriate and possible (about 2.6 million houses), will annually consume 1.7 x 10(4) (6.4 x 10(3) to 3.9 x 10(4)) TJ of end-use energy, cost $230 (130 to 400) million (at current energy prices), and generate 2.0 x 10(9) (1.2 x 10(9) to 3.5 x 10(9)) kg of CO2. Passive or energy efficient radon mitigation systems currently being developed offer opportunities to substantially reduce these impacts.