The aim of this study was to compare the clinical outcome of three different medications (ivermectin injection, canaural eardrops and frontline combo) in treatment of ear mite infestation accompanied by otitis externa in cats using a randomized trial. Cases presented to the Small Animal Clinic, Faculty of Veterinary Medicine, Assiut University for investigating signs of ear mite infestation and/or otitis externa were recruited (n=17) and randomly assigned to one of the 3 groups for evaluation of response to treatment over a period of 30 days. Cases that did not respond to treatment within 2 weeks of treatment were changed to one of the other two medication. A simple questionnaire was designed to evaluate owner satisfaction of the medication price, ease of administration, cat tolerance and improvement of signs. Recruited cases were either brought to the clinic for re-evaluation or the owner was contacted by phone to evaluate progress of each case. In the ivermectin-treated group (Group 1; n=7), 75% of cases recovered from ear mite infestation based on signs resolving and disappearance of presenting signs. Only 60% of cases treated with frontline (Group 2) showed an improvement of signs (n=5). All cases treated with Canaural (Group 3) showed complete recovery with complete absence of presenting signs and signs of otitis externa (n=5). Average age of cats in all groups ranged from two to 72 months (mean= 17.33, median=6.5). Statistically there were no significant difference between the three medications (p>0.5), but according to the clinical findings, we can suggest that Canaural is the most suitable when otitis externa is present along with ear mite infestation. Frontline Combo is not as effective as the two other medications used in this study