Abstract Sequestration of anthropogenic “greenhouse gases” such as CO 2 is proposed as a means of reducing global warming. We tested the possibility of sequestering CO 2 in regional-scale aquifers in sedimentary basins, including residence time in possible aquifer storage sites and migration rates away from such sites. The example basin studied is the Powder River Basin, Wyoming. We calibrated regional scale rock properties in the Powder River Basin using surface heat flow observations. We determined advection by a regional-scale groundwater flow system in the basin can explain anomalously high surface heat flow not explained by conduction alone. Our study suggests that regional scale sedimentary basin aquifers are viable candidates for CO 2 sequestration for time-scales of 10 3 years.