Use of agricultural subsurface drainage systems in the Prairie Pothole Region of North America continues to increase, prompting concerns over potential negative effects to the Region's vital wetlands. The U.S. Fish and Wildlife Service protects a large number of wetlands through conservation easements that often utilize standard lateral setback distances to provide buffers between wetlands and drainage systems. Because of a lack of information pertaining to the efficacy of these setback distances for protecting wetlands, information is required to support the decision making for placement of subsurface drainage systems adjacent to wetlands. We used qualitative graphical analyses and data comparisons to identify characteristics of subsurface drainage systems and wetland catchments that could be considered when assessing setback distances. We also compared setback distances with catchment slope lengths to determine if they typically exclude drainage systems from the catchment. We demonstrated that depth of a subsurface drainage system is a key factor for determining drainage setback distances. Drainage systems located closer to the surface (shallow) typically could be associated with shorter lateral setback distances compared with deeper systems. Subsurface drainage systems would be allowed within a wetland's catchment for 44–59% of catchments associated with wetland conservation easements in North Dakota. More specifically, results suggest that drainage setback distances generally would exclude drainage systems from catchments of the smaller wetlands that typically have shorter slopes in the adjacent upland contributing area. For larger wetlands, however, considerable areas of the catchment would be vulnerable to drainage that may affect wetland hydrology. U.S. Fish and Wildlife Service easements are associated with > 2,000 km² of wetlands in North Dakota, demonstrating great potential to protect these systems from drainage depending on policies for installing subsurface drainage systems on these lands. The length of slope of individual catchments and depth of subsurface drainage systems could be considered when prescribing drainage setback distances and assessing potential effects to wetland hydrology. Moreover, because of uncertainties associated with the efficacy of standard drainage setback distances, exclusion of subsurface drainage systems from wetland catchments would be ideal when the goal is to protect wetlands.