The objective of the present study was to evaluate the clinical effectiveness and safety of the local application of triderm for the treatment of diffuse external otitis. The study included 68 patients presenting with bacterial and fungal diffuse external otitis. The treatment in the form of local empiric therapy was continued till the results of microbiological treatment became apparent. The beneficial outcome achieved in 91.2% of the patients was clinically manifest as the regression of the inflammatory process in the external auditory meatus. No complications, such as ototoxic events, either local or systemic allergic reactions, were documented. The authors substantiate the possibility of the application of the medication under consideration for the treatment of diffuse external otitis based on the knowledge of the mechanism of the actin of its constituent components, viz. betamethasone, dipropionate, gentamicin sulfate, and clotrimazole, taking into account the occurrence of the most common causative agents of diffuse external otitis. It is concluded that triderm is a safe medication for the local application and, probably, for the initial empiric therapy of diffuse external otitis to be continued till the results of the microbiological treatment become apparent.