Plague is a flea-borne disease of mammalian hosts. On the grasslands of western North America, plague stifles populations of Cynomys spp. prairie dogs (PDs). To manage plague, PD burrows are treated with 0.05% deltamethrin dust that can suppress flea numbers and plague transmission. Here, we evaluate the degree and duration of deltamethrin flea control with three PD species at six sites across four U.S. states. Data were simultaneously collected at paired plots. Burrows from one randomly assigned member of each pair were treated with deltamethrin; non-treated plots served as experimental baselines. Flea control was strong ≤two months after treatment, remained moderate one year later, and was statistically detectable for up to two years at some sites. Flea abundance was lower in plots with higher rates of deltamethrin application. After burrow treatments, flea abundance increased over time, reaching >one per PD within 255 to 352 days. Nevertheless, annual treatments of burrows with deltamethrin provided PDs with substantial protection against plague. Even so, deltamethrin should be further evaluated and combined with other tools under an integrated approach to plague management. Integrated plague management should help to conserve PDs and species that associate with them, including the endangered black-footed ferret (Mustela nigripes).