Otodectes cynotis is a contagious ear mite generally responsible of a parasitic otitis. This prospective study evaluates the efficacy, safety and impact on quality of life (QoL) of oral lotilaner for the treatment of Otodectes infestation in ferrets. Ferrets of weight greater than 500 g, with Otodectes mites confirmed on ear swabs examination and that did not receive an acaricidal treatment in the previous two weeks were included. Oral lotilaner (Credelio 12 mg, ELANCO FRANCE, Sèvres, France) was administered at inclusion day (D0) and 28 days later (D28). Parasitic counts and clinical examination were performed at D0, D28 and D56. A QoL and owner satisfaction questionnaire was given at D0 and D56. Statistical analysis was performed with Shapiro-Wilk test for normality and Wilcoxon test for mean comparison (significance: p<0.05). Eleven ferrets were included, two were asymptomatic. Mean weight was 1.2 kg (0.68-2.66). Mean lotilaner dose was 12.3 mg/kg (9-17.6). Mean eggs, adults or nymphs, larvae, and fragments counts were 30.4 (3-104), 11.2 (1-61), 5.4 (0-36), 3.5 (1-7) respectively at D0; 0, 0, 0.1 (0-1), 0.5 (0-3) respectively at D28; 0, 0, 0, 0.14 (0-1) respectively at D56. Differences were statistically significant from baseline in all cases (p<0.05). Pruritus was absent in all cases at D56. No adverse effects were reported. All owners were "completely satisfied" with the treatment. Mean impact of the disease on QoL was 4.5/18 (SD=4.15) at D0 and 0 at D56 (significant difference, p<0.05). Oral lotilaner appears as a safe, efficient, easy to use and satisfactory treatment of Otodectes cynotis infestation in ferrets.