Subsurface tile drainage is a major contributor of NO3–N from cropland in the Upper Midwest to the hypoxic zone in the Gulf of Mexico. Strategies to reduce NO3–N loadings to the Gulf of Mexico require better understanding of the effects of tile spacing and depth on subsurface tile drainage and NO3–N losses from subsurface tile drained fields. This study evaluated the sensitivity of NO3–N losses to changes in the spacing and depth of subsurface tile drainage systems. For this purpose, the Agricultural Drainage and Pesticide Transport (ADAPT) model was calibrated and validated using monthly subsurface tile drainage and NO3–N losses measured in tile drains during 1999 to 2003 from two commercial fields (west and east) in south-central Minnesota. For the calibration period, there was good agreement between observed and predicted subsurface tile drainage and NO3–N losses, with Nash–Sutcliffe modeling efficiencies of 0.75 and 0.56, respectively. Better agreements were observed for the validation periods. The calibrated model was used to evaluate the effects of tile drain spacing and depth with a 50-yr record (1954–2003) of daily precipitation. Simulation results indicated that reductions in NO3–N losses are possible by decreasing the depth or increasing the spacing of tile drains. For instance, for a tile drain spacing of 40 m, reducing the drain depth from 1.5 to 0.9 m reduced NO3–N losses by 31% (but reduced crop yield by 60%), while for a tile drain depth of 1.5 m, increasing the tile drain spacing from 27 to 40 m reduced NO3–N losses by 50% (while reducing crop yield by 7%). Increased tile drain spacing or decreased tile drain depth could be a potential remedy for excess NO3–N loadings entering the Gulf of Mexico.