Japanese barberry (Berberis thunbergii de Candolle; Ranunculales: Berberidaceae) is an exotic shrub that has invaded woodland understories in the northeastern United States. It forms dense thickets providing ideal structure and microclimate for questing blacklegged ticks (Ixodes scapularis Say; Acari: Ixodidae). While there have been studies on the favorable habitat barberry provides blacklegged ticks, little has been studied on the relationship between barberry, vectors (ticks), and reservoirs (white-footed mice; Peromyscus leucopus Rafinesque; Rodentia: Cricetidae); specifically, the influence Japanese barberry has on the abundance of blacklegged ticks and Borrelia burgdorferi infection (Johnson, Schmid, Hyde, Steigerwalt, and Brenner; Spirochaetales: Spirochaetaceae) in mice. We studied the impacts of barberry treatment over the course of 6 yr to determine influence on encounter abundance with white-footed mice, encounter abundance with B. burgdorferi-infected mice, and juvenile blacklegged ticks parasitizing mice. Results from our study suggest that while both white-footed mouse and B. burgdorferi-infected mouse encounters remained similar between barberry treatment areas, juvenile tick attachment to mice was significantly greater in intact barberry stands (X¯ = 4.4 ticks per mouse ± 0.23 SEM) compared with managed (X¯ = 2.8 ± 0.17; P < 0.001) or absent (X¯ = 2.2 ± 0.16; P < 0.001) stands. Results of this study indicated that management of barberry stands reduced contact opportunities between blacklegged ticks and white-footed mice. Continued efforts to manage Japanese barberry will not only allow for reestablishment of native plant species, but will also reduce the number of B. burgdorferi-infected blacklegged ticks on the landscape.