Nitrate concentration and stream discharge data from USGS National Stream Quality Accounting Network monitoring stations in the upper Mississippi River (UMR) and Ohio River basins were used to calculate stream nitrate loading and annual flow-weighted average (FWA) nitrate concentrations. The model accounts for 90% of the variation among stations in long term FWA nitrate concentrations and was used to estimate FWA nitrate concentrations for a 100 ha grid across the UMR and Ohio River basins. To estimate potential nitrate removal by wetlands across the same grid area, mass balance simulations were used to estimate percent nitrate reduction for hypothetical wetland sites distributed across the UMR and Ohio River basins. Modeling results suggest that a 30% reduction in nitrate load from the UMR and Ohio River basins could be achieved using 210,000-450,000 ha of wetlands targeted on the highest nitrate contributing areas.