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In Alberta, Canada (1982-2001), and in Idaho, Montana, and Wyoming, United States (1987-2001), wolves (Canis lupus) killed various domestic animals, among which the major prey were sheep in the United States (68%, n = 494) and cattle in Canada (95%; n = 1633). Under recovery programs, the wolf population increased in the United States, and depredation events increased proportionately. In both countries, the number of domestic animals killed each year was correlated with the number of wolves killed by government authorities for depredation management. We tested the ability of anti-wolf barriers made of flags hanging from ropes to impede wolf access to food and livestock. In 18 experiments, barriers prevented captive wolves (n = 9) from accessing food for up to 28 hours and allowed daily separation of wolves to administer contraceptive pills to a female wolf. Barriers prevented access by wild wolves to 100-m2 baited sites during two 60-day tests. We also set barriers around three cattle pastures. In Alberta during two 60-day trials on 25-ha pastures, wolves approached barriers on 23 occasions but did not cross them, and no cattle were killed. Wolves killed cattle on neighboring ranches during the trials and before and after the trials on the tested ranches. In Idaho four radio-collared wolves crossed barriers and killed cattle in a 400-ha ranch after 61 days of barrier exposure. Our results suggest that anti-wolf barriers are effective in deterring captive and wild wolves for >1 and ≥60 days, respectively, and that wild wolves switch to alternative livestock when excluded from one herd of livestock. Our depredation data indicate that protecting livestock from wolves reduces the necessity for killing wolves. Barriers could play a role among the limited set of preventive measures available and offer a cost-effective mitigation tool for the problem of livestock depredation on a local scale.