Objectives: To date, there is no consensus regarding a particular treatment agent that might be the most efficacious for eradication of otomycosis. Our objective was to determine the effectiveness and safety profile of the most commonly used agents in the treatment of otomycosis, as well as highlight the safety profile of the various treatment options. Data sources: PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews databases. Methods: Literature search by 2 independent authors was conducted using the abovementioned databases. Studies of various agents used for otomycosis treatment in adult patients were included. A meta-analysis was conducted to compare treatment efficacy among various treatment agents included. In addition, subgroup meta-analysis on the most commonly used drugs: 1% topical clotrimazole, miconazole cream, and fluconazole drops was performed. Results: A total of 15 randomized controlled trials (RCTs) with a total of 2309 patients diagnosed with otomycosis were included in this study. The meta-analysis demonstrated an average eradication rate of 73.6%. Subgroup meta-analysis revealed that the efficacy of complete eradication ranged from 29.0% to 98.3%. Adverse effects noted were overall low, and were mainly otalgia, pruritus, and burning sensation in the ear. Conclusion: The current review demonstrated a >70% rate of complete otomycosis eradication among all topical therapies, with clotrimazole being among the most commonly used treatment options. However, future well-designed studies with unified protocols are needed to ensure homogeneity of findings and to be able to solidify these findings, as well as to ascertain the ototoxicity of agents used.