Background -Otodectes cynotis (ear mite) accounts for 50-80% of cases of otitis externa in cats. Various treatment options exist but evidence-based reviews on treatments for this parasite have not been conducted.Hypothesis/Objectives -The purpose of this study was to systematically review the efficacy of treatments for Otodectes cynotis infestation in cats, to provide recommendations for their use and to suggest methodologies for future clinical trials and research.Methods -Electronic searches were carried out using the PubMed, CAB Direct and Thomson Reuters Web of Science; relevant topics were hand searched. The review was restricted to peer reviewed articles without limitation of language and publication date; only in vivo studies were included. The data were extracted and tabulated, then compared with regard to study design. With only a few randomized and controlled trials (RCTs) available, it was not possible to perform a meta-analysis of the pooled data.Results -A total of 27 trials published between 1978 and 2015 fulfilled the selection criteria; 17 different pharmacological interventions were identified. There were two blinded RCTs and 25 open uncontrolled trials.Conclusions and clinical importance -There is fair evidence for recommending spot-on 10% imidacloprid +1% moxidectin or selamectin, once or twice 30 days apart, while there is insufficient evidence for or against recommending all other medications due to the quality of study designs in spite of their high efficacies. Future blinded RCTs, using placebo or appropriate active drugs, are required; outcome measurements on both clinical and microbiological and parasitological improvement, and proper follow-up periods are recommended.