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Background: Otitis externa is an inflammatory in external auditory canal, with the presentation of otalgia, otorrhea, and pruritus. Bacteria and fungi are the most causative agents of the disease. Although several antifungal and antibacterial agents are usually used to treat it, combination therapy plays an important role in good treatment efficacy. Objectives: According to the problems associated with the treatment of mixed otitis externa, the current study aimed at evaluating the efficacy of ceftazidime powder and topical miconazole (as the case group) versus topical miconazole only (as the control group) to treat mixed otitis externa. Methods: Seventy-two patients with mixed otitis externa were divided into two groups; the case group was treated with ceftazidime powder and topical miconazole, and the control group was treated only with topical miconazole. Both groups were evaluated after two weeks. The diagnosis of mixed otitis externa was based on signs, symptoms, and the presence of bacterial and fungal elements in direct examination and culture. Results: Swelling, itching, and canal discharge were observed in 67.7%, 64.7%, and 90.3% of the patients, respectively in the case group, and 47.1%, 26.3% and 93.1% of the patients, respectively in the control group. Complete resolution of all clinical signs and symptoms occurred in 23 (67.6%) patients in the case group and 11 (28.9%) patients in the control group (P = 0.001). Staphylococcus epidermidis and Pseudomonas aeruginosa were the most common bacteria, and Aspergillus spp. and Candida spp. were the most common fungi identified in the cultures. Conclusions: According to the complete resolution of clinical signs, the application of ceftazidime powder and topical miconazole was better than topical miconazole to treat mixed otitis externa.