A study was conducted to assess the efficacy of drainage setbacks for limiting effects to wetlands in the Prairie Pothole Region, USA. Surface-water levels, along with primary components of the wetland water balance, were monitored at four wetland catchments over 3 years. During the second year of the study, subsurface drainage systems were installed in two of the wetland catchments using drainage setbacks, and the drainage discharge volumes were monitored. A catchment water-balance model also was used to assess the potential effect of subsurface drainage (i.e., reduced precipitation runoff) on wetland hydrology, and to assess the efficacy of drainage setbacks for mitigating these effects. These data directly support the associated publication “A case study examining the efficacy of drainage setbacks for limiting effects to wetlands in the Prairie Pothole Region, USA” which is referenced within the Metadata.