Accurate characterization of wetland condition at a regional or watershed scale requires an assessment that includes both a quantity and quality component. A probabilistic sampling design can facilitate the implementation of such assessments through its ability to extrapolate results from a random sample of wetlands to the entire population of wetlands over a large geographic area. In 2003 an assessment of the quantity and quality of depressional wetlands in the Redwood River watershed was conducted using a probabilistic sampling design. The number and cumulative area of depressional wetlands in the watershed was estimated relative to the National Wetland Inventory (NWI) by evaluating 146 randomly selected sites. However, limitations of the study design only allowed quantification of wetland loss over the ∼20-year period (c.1980–2003) following the acquisition of aerial imagery used to produce the NWI in this region. Wetland quality was assessed in 40 randomly selected sample sites using plant and macroinvertebrate indices of biological integrity (IBI). Depressional wetlands included in the NWI have experienced an estimated 56% reduction in number, equivalent to a 21% decrease in area, in the watershed over the last 20 years. Of the remaining wetland area, an estimated 91% was impaired. Thus, management practices with the goal of increasing suitable habitat for native wetland plant and animal communities should focus on restoration of drained wetlands as well as improvement of existing wetlands to maximize outcomes.