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Background: The clinical efficacy of fluralaner chewable tablets (Bravecto™, MSD Animal Health) against naturally acquired Linognathus setosus infestations on dogs was evaluated compared with permethrin (Exspot®, MSD Animal Health) treatment. Methods: Privately-owned dogs naturally infested with L. setosus from 21 different households were randomly allocated to two treatment groups. Fourteen dogs were treated once orally with fluralaner and ten dogs were treated once topically with permethrin, at the recommended label dose. Live L. setosus on all dogs were counted before treatment and 1, 7, 28 (both groups) and 84 (fluralaner group) days post-treatment according to a coat parting technique at pre-specified locations and lice species were confirmed microscopically. At the same time points, a veterinary dermatology severity score and an owner's perceived pruritus score were recorded. Results: Percentage reduction in geometric mean L. setosus counts, comparing post-with pre-treatment counts within each group, were 85.7% (day 1), 96.8% (day 7) and 100% (days 28 and 84) for the fluralaner (two-sided two-sample t-test, P ≤ 0.0088 for days 1-84) and 67.5% (day 1), 90.3% (day 7) 99.1% (day 28) for the permethrin group (two-sided two-sample t-test, P ≤ 0.0014 for days 7-28). No lice were seen on fluralaner-treated dogs 28 and 84 days post-treatment. In contrast, two permethrin-treated dogs were re-treated at 7 and 28 days after initial treatment because of observed lice. Owner's perceived pruritus scores were reduced compared to pre-treatment levels by 23.8% (day 1), 31.1% (day 7), 70.4% (day 28) and 99.5% (day 84) after fluralaner treatment and 21.3% (day 1), 45.8% (day 7), and 78.1% (day 28) after permethrin treatment. Dermatological signs were improved compared to pre-treatment levels in both treatment groups. Conclusions: Single oral fluralaner treatment eliminated natural L. setosus infestation on dogs within 28 days and led to complete dermatological recovery that was maintained until the study end on day 84. Single topical permethrin treatment reduced the number of L. setosus by 99.1% at day 28 although two animals required unscheduled re-treatment. [ABSTRACT FROM AUTHOR]