Wildlife–vehicle collisions, especially with deer (Odocoileus spp.), elk (Cervus elaphus), and moose (Alces alces) are numerous and have shown an increasing trend over the last several decades in the United States and Canada. We calculated the costs associated with the average deer–, elk–, and moose–vehicle collision, including vehicle repair costs, human injuries and fatalities, towing, accident attendance and investigation, monetary value to hunters of the animal killed in the collision, and cost of disposal of the animal carcass. In addition, we reviewed the effectiveness and costs of 13 mitigation measures considered effective in reducing collisions with large ungulates. We conducted cost–benefit analyses over a 75-year period using discount rates of 1%, 3%, and 7% to identify the threshold values (in 2007 U.S. dollars) above which individual mitigation measures start generating benefits in excess of costs. These threshold values were translated into the number of deer–, elk–, or moose–vehicle collisions that need to occur per kilometer per year for a mitigation measure to start generating economic benefits in excess of costs. In addition, we calculated the costs associated with large ungulate–vehicle collisions on 10 road sections throughout the United States and Canada and compared these to the threshold values. Finally, we conducted a more detailed cost analysis for one of these road sections to illustrate that even though the average costs for large ungulate–vehicle collisions per kilometer per year may not meet the thresholds of many of the mitigation measures, specific locations on a road section can still exceed thresholds. We believe the cost–benefit model presented in this paper can be a valuable decision support tool for determining mitigation measures to reduce ungulate–vehicle collisions.