Vole (Cricetidae) girdling of tree trunks is a common form of damage experienced by tree and vine growers throughout much of the Northern Hemisphere. Management programs that effectively incorporate chemical repellents and vegetation management would be of substantial assistance to growers that experience such damage. Anthraquinone has proven effective as a repellent against voles in lab trials, yet controlled field tests of combined anthraquinone and vegetation management programs are lacking. Therefore, we established a mesocosm-based study in central California, USA, to test the efficacy of anthraquinone and vegetation management for reducing girdling damage caused by California voles Microtus californicus to Clementine citrus trees Citrus clementine under semi-field conditions. We observed a 90–100% reduction in girdling damage for trees following a single application of anthraquinone during two trials in summer and spring, respectively. Removal of vegetation around the base of trees further reduced damage during the summer sampling period, with no girdling observed on anthraquinone-treated trees that were surrounded by bare soil. We did not observe this same relationship during spring, and we observed no relationship between vegetation management in the absence of anthraquinone treatments in either seasonal trial, suggesting that vegetation management had a lesser impact on vole girdling than anthraquinone applications. We observed no decrease in efficacy of anthraquinone across the duration of both sampling periods (5–6 weeks), indicating substantial longevity for anthraquinone. Anthraquinone appears to have substantial utility for minimizing vole girdling damage. Field testing is warranted for additional mammalian species to determine potential uses for other taxa.