Background: Numerous therapeutic modalities have been used either singly or in combination to treat recalcitrant warts. However, a single treatment that is entirely effective in all patients is not yet explored. This might be attributed to the absence of specific antiviral medications against human papilloma virus (HPV) infection. Objective: The aim of this work was to compare efficacy of intralesional vitamin D3 in treatment of plantar warts in comparison to candida albicans antigen. Patients and methods: This study included a total of 40 patients suffering from plantar warts, attending at Dermatology and Andrology Outpatient Clinic, Dermatology Department, Al-Azhar University Hospitals. The included subjects were randomly divided into two groups; Group A (Candida antigen group) consisted of 20 patients, subjected to intralesional injection of candida albicans antigen and Group B: (Vitamin D3 group) consisted of 20 patients, subjected to intralesional injection of Vitamin D3. Results: Results revealed that there were no statistically significant correlations between age, sex of patients, duration of treated warts and clinical response in both treatment groups. However, a statistically significant correlation existed between the number of treated warts and response in Vitamin D group. Complete response occurred in patients with low number of warts. At the end, our results showed that there was no statistically significant correlation in complete response between candida antigen and vitaminD3. Both treatments show comparable efficacy and safety in treatment of plantar warts. Conclusion: Treatment of multiple warts by intralesional injection of candida antigen or vitamin D3 is safe and effective, with good cure rates, excellent safety profile and minimal recurrences.