The enhancement of agricultural lands through the use of artificial drainage systems is a common practice throughout the United States, and recently the use of this practice has expanded in the Prairie Pothole Region. Many wetlands are afforded protection from the direct effects of drainage through regulation or legal agreements, and drainage setback distances typically are used to provide a buffer between wetlands and drainage systems. A field study was initiated to assess the potential for subsurface drainage to affect wetland surface-water characteristics through a reduction in precipitation runoff, and to examine the efficacy of current U.S. Department of Agriculture drainage setback distances for limiting these effects. Surface-water levels, along with primary components of the catchment water balance, were monitored over 3 y at four seasonal wetland catchments situated in a high-relief terrain (7–11% slopes). During the second year of the study, subsurface drainage systems were installed in two of the catchments using drainage setbacks, and the drainage discharge volumes were monitored. A catchment water-balance model was used to assess the potential effect of subsurface drainage on wetland hydrology and to assess the efficacy of drainage setbacks for mitigating these effects. Results suggest that overland precipitation runoff can be an important component of the seasonal water balance of Prairie Pothole Region wetlands, accounting on average for 34% (19–49%) or 45% (39–49%) of the annual (includes snowmelt runoff) or seasonal (does not include snowmelt) input volumes, respectively. Seasonal (2014–2015) discharge volumes from the localized drainage systems averaged 81 m³ (31–199 m³), and were small when compared with average combined inputs of 3,745 m³ (1,214–6,993 m³) from snowmelt runoff, direct precipitation, and precipitation runoff. Model simulations of reduced precipitation runoff volumes as a result of subsurface drainage systems showed that ponded wetland surface areas were reduced by an average of 590 m² (141–1,787 m²), or 24% (3–46%), when no setbacks were used (drainage systems located directly adjacent to wetland). Likewise, wetland surface areas were reduced by an average of 141 m² (23–464 m²), or 7% (1–28%), when drainage setbacks (buffer) were used. In totality, the field data and model simulations suggest that the drainage setbacks should reduce, but not eliminate, impacts to the water balance of the four wetlands monitored in this study that were located in a high-relief terrain. However, further study is required to assess the validity of these conclusions outside of the limited parameters (e.g., terrain, weather, soils) of this study and to examine potential ecological effects of altered wetland hydrology.