Acquisition of perpetual grassland easements is a principal tactic used by the United States Fish and Wildlife Service (USFWS) and its partners to protect nesting habitat for migratory birds in the Prairie Pothole Region of North and South Dakota, USA. This public-private partnership resulted in the conservation of >344,000 ha of grassland during 1998-2012. Past easement acquisition has been targeted to landscapes with greatest expected accessibility to breeding duck pairs without active consideration of probability of conversion or cost of protection. The rising cost of easement acquisition in recent years indicates that re-evaluation and refinement of the easement acquisition strategy could help to improve programmatic outcomes. We assessed regional patterns of easement acquisition during 1998-2012, evaluated the current targeting strategy, and used a combination of publicly available and proprietary geospatial data to develop an easement-targeting Geographic Information System that integrated information about conversion probability and protection cost with current targeting criteria. Our assessment indicated that grassland protection was negatively affected by rising land prices during 1998-2012. In the 5 y between 2008 and 2012, about 100,000 ha of grassland were protected at a cost of $83 million (U. S. dollars). The 2008-2012 acquisitions represented 30% of total protection during 1998-2012 but composed 47% of the total expenditure. We observed strong evidence that easements were targeted to priority landscapes both before and after formalization of the USFWS conservation strategy in 2004. We also found evidence of an opportunity to increase efficiency of future acquisitions. We identified 0.9 million ha of currently unprotected priority grassland in the region with greater than expected conversion risk and smaller than expected protection cost. We suggest that future grassland easement acquisition be refocused on this refined priority area and that an adaptive approach to future easement acquisition (including targeted acquisitions, directed monitoring, and data-based decisions) provides a logical framework for implementation of this new strategy and will facilitate continued conservation success.