Purpose: Various agents with various antifungal properties are widely used for otomycosis eradication. However, there is still no consensus on the most effective agent. Therefore, the present study aims to investigate the efficacy of topical 1% isoconazole nitrate cream in the treatment of otomycosis. Methods: This prospective study included 43 patients who were applied to our outpatient clinic with complaints of ear pain, itching, aural fullness, and hypoacusis, and were diagnosed with unilateral otomycosis. After aspiration and cleaning, the external ear canal was filled with 1% isoconazole nitrate cream using an iv cannula and insulin syringe. Control examinations were performed on the 5th, 10th, 15th, and 20th days. In the follow-up examinations, patients were asked about how many days after the cream administration the pain and itching completely relief and the answers were recorded. Results: In the first control examination of 23 (92%) of 25 patients with pain, it was observed that the pain and otoendoscopic examination findings completely recovered. In the second control, it was found that both pain and otoendoscopic examination findings completely recovered in the remaining 2 patients (25 patients, 100%). 35 patients complained of itching and it was observed that itching and otoendoscopic examination findings completely recovered in 26 patients (75%) in the first control, 5 more patients (31 patients, 88.6%) in the second control, and 2 more patients (33 patients, 94.3%) in the third control examination. Conclusion: Isoconazole nitrate cream appears to be an effective and easily applicable agent for the treatment of otomycosis.