Background: The current study aimed to determine the efficacy and safety of honey in the treatment of persistent chronic otitis externa. Patients and methods: This randomized-controlled study was conducted in Helwan and Banha Medical Universities Hospitals, Egypt in the period 2014-2016. Eligible patients were randomly allocated to the study group and the control group. For the study group, Honey ear drops 1 ml was used, and for the control group undiluted glycerol was used. The primary outcome measure was the number of organisms in tenfold diluted broth culture in after the treatment period. Results: A Hundred patients were included in the analysis, 50 in each group. The two groups were comparable regarding the baseline characteristics. At the end of the study, there was a highly significant difference in the number of organisms in tenfold diluted broth culture between groups (p-value < 0.001) where it was 34.28(9.37) & 58.98 (11.44) in the Honey groups and the Placebo group, respectively. Moreover, improvements in patients’ symptoms (discomfort, itchiness, wetness, and smell) were significantly higher in the Honey group than in the Placebo group. Also, improvements of signs (erythema, ulceration, granulation and discharge quantity) were significantly higher in the Honey group than in the Placebo group. There were no adverse events for the Honey drops. Conclusions: Honey is effective as ear drops for persistent chronic otitis externa.