Endemic animal diseases such as tsetse-transmitted trypanosomosis are a constant drain on the financial resources of African livestock keepers and on the productivity of their livestock. Knowing where the potential benefits of removing animal trypanosomosis are distributed geographically would provide crucial evidence for prioritising and targeting cost-effective interventions as well as a powerful tool for advocacy. To this end, a study was conducted on six tsetse-infested countries in Eastern Africa: Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda. First, a map of cattle production systems was generated, with particular attention to the presence of draught and dairy animals. Second, herd models for each production system were developed for two scenarios: with or without trypanosomosis. The herd models were based on publications and reports on cattle productivity (fertility, mortality, yields, sales), from which the income from, and growth of cattle populations were estimated over a twenty-year period. Third, a step-wise spatial expansion model was used to estimate how cattle populations might migrate to new areas when maximum stocking rates are exceeded. Last, differences in income between the two scenarios were mapped, thus providing a measure of the maximum benefits that could be obtained from intervening against tsetse and trypanosomosis. For this information to be readily mappable, benefits were calculated per bovine and converted to US$ per square kilometre. Results indicate that the potential benefits from dealing with trypanosomosis in Eastern Africa are both very high and geographically highly variable. The estimated total maximum benefit to livestock keepers for the whole of the study area amounts to nearly US$ 2.5 billion, discounted at 10% over twenty years – an average of approximately US$ 3300 per square kilometre of tsetse-infested area – but with great regional variation from less than US$ 500 per square kilometre to well over US$ 10,000. The greatest potential benefits accrue to Ethiopia, because of its very high livestock densities and the importance of animal traction, but also to parts of Kenya and Uganda. In general, the highest benefit levels occur on the fringes of the tsetse infestations. The implications of the models’ assumptions and generalisations are discussed.