Background: The endemic vector-borne diseases transmitted by tsetse and ticks impose heavy burdens on the livestock keepers in Africa. Applying deltamethrin to the belly, legs, and ears of cattle offers a possibility of mitigating these losses at a cost affordable to livestock keepers. Although studies have quantified the impacts of individual diseases on livestock productivity, little is known about the dual economic benefits of controlling both tsetse and ticks, nor about the number of cattle that need to be treated to confer these benefits. Alongside an epidemiological study in south-east Uganda, a farm level assessment was done to investigate the benefits and costs of spraying different proportions of the village cattle population using this restricted application protocol.Methods: A study comprising 1,902 semi-structured interviews was undertaken over a period of 18 months. Financial data on household income and expenditure on cattle was collected, and cost-benefit analysis was done pre- and post-intervention and for different spraying regimes. The total cost of the intervention was obtained from the implementation costs of the epidemiological study and from expenses incurred by participating farmers enabling examination of benefit-cost ratios and incremental benefit-cost ratios for each treatment regime.Results: The benefit-cost analysis of spraying 25%, 50%, and 75% of the cattle population yielded average benefit-cost ratios of 3.85, 4.51, and 4.46. The incremental benefit-cost ratios from spraying each additional 25% of the cattle population were 11.38, 3.89, and 0.79, showing a very high return on investment for spraying 50% of the population, with returns reducing thereafter.Conclusion: Comparing the gross margins per bovine, the study found that increasing the proportion of cattle sprayed yielded increasing benefits to the farmers, but that these benefits were subject to diminishing returns. From a practical viewpoint, this study recommends spraying only draft cattle to control trypanosomiasis and tick-borne diseases in this area as they make 38.62% of the cattle population, approaching the 50% threshold. In areas with a lower proportion of draft males, farmers could be advised to also include cows.