INTRODUCTION: Otomycosis is a common diseases that can be associated with many complications including involvement of the inner ear and mortality in rare cases. Management of otomycosis can be challenging, and requires a close follow-up. Treatment options for otomycosis include local debridement, local and systemic antifungal agents and utilization of topical antiseptics. OBJECTIVE: This study was designed to compare the recovery rate of otomycosis using two therapeutic methods; topical betadine (Povidone-iodine) and clotrimazole. METHODS: In this single-blind clinical trial, 204 patients with otomycosis were selected using a non-probability convenient sampling method and were randomly assigned to two treatment groups of topical betadine and clotrimazole (102 patients in each group). Response to treatment was assessed at 4, 10 and 20 days after treatment. Data were analyzed using the independent t-test, Chi-Square and Fisher exact test in SPSS v.18 software, at a significance level of p<0.05. RESULTS: The results showed that out of 204 patients with otomycosis, fungi type isolated included Aspergillus in 151 cases (74%), and Candida albicans in 53 patients (26%). On the fourth day after treatment, 13 patients (13.1%) in the group treated with betadine and 10 patients (9.8%) in the group treated with clotrimazole showed a good clinical response to treatment (p=0.75). A good response to treatment was reported for 44 (43.1%) and 47 patients (46.1%) on the tenth day after the treatment (p=0.85); and 70 (68.6%) and 68 patients (67.6%) on the twentieth day after treatment (p=0.46) in the groups treated with betadine and clotrimazole, respectively. The response to treatment was thus not significantly different in the two groups. CONCLUSION: In the present study the efficacy of betadine and clotrimazole was the same for the treatment of otomycosis. The result of this study supports the use of betadine as an effective antifungal in otomycosis treatment, helping to avoid the emergence of resistant organisms.