BackgroundGeneralized demodicosis is a common disease in dogs and doramectin has been reported as a successful treatment. Different treatment protocols using doramectin have not been previously evaluated.ObjectiveTo evaluate whether oral administration of doramectin twice a week is more effective than administration by subcutaneous injection once a week.AnimalsTwenty nine privately owned dogs affected with generalized demodicosis.MethodsDogs randomly received one of two treatments. Sixteen dogs were treated with 600 μg/kg doramectin by subcutaneous injection once a week and 13 dogs received 600 μg/kg doramectin by oral administration twice a week.ResultsThe mean age of affected dogs was 2.8 and 2.6 years (P= 0.587) and the mean mite number detected at the initial evaluation was 201 and 287 (P= 0.04), respectively, for each group. The mean time to achieve negative skin scrapings was 13 and 12 weeks, respectively (P= 0.955). Adult‐onset demodicosis affected five of 16 and two of 13 dogs, respectively (P= 0.662). The success rate for treatment was 13 of 16 (81%) of dogs receiving subcutaneous injections once a week and 12 of 13 (92%) dogs receiving oral dosaging twice a week. (P= 0.691). Four dogs did not achieve disease remission. In the 12 month follow‐up period, one dog that had received the once a week protocol relapsed after eight weeks of treatment withdrawal. Adverse effects were not observed in any dog.ConclusionBased on the results of this study, oral administration of doramectin twice a week does not achieve a more rapid resolution of canine generalized demodicosis than administration by subcutaneous injection once a week. The treatment success rate was the same for both protocols.