Background: Viral warts are caused by human papillomavirus. Many therapeutic options are available for treating warts. Newer and effective treatments include intralesional immunotherapy, has been tried in the recent times with variable success rates. Objective: The aim of this study was to compare the effect of intralesional vitamin D3 versus purified protein derivative (PPD) in the treatment of multiple cutaneous warts. Methods: A total of 62 patients were included in the study, each patient had at least 3 common warts, one or more of them injected with 0.1 of intralesional PPD, one or more injected with 0.5 of vitamin D3 and one or more were control according to number of warts of each patient and up to 4 sessions. The clinical assessment was done by photographic measurements at baseline, before each treatment session, and after the completion of treatment. Results: In PPD-injected lesions. 43 patients (69.4%) showed complete clearance (100%) and 13 patients (20.9%) showed partial response (25% - 99%). While, in vitamin D3-injected lesions, 22 patients (35.5%) showed complete clearance while 21 patients (33.9%) showed partial response. On comparing between PPD, vitamin D3 and control, both PPD and vit D3 were statistically significant compared to control and PPD was more statistically significant than vit D3 (P3 = 0.019) in effectiveness and less in recurrence rate. Conclusions: PPD and vitamin D3 were found to be effective, well-tolerated modalities of treatment of multiple common warts. Intralesional PPD was more statistically significant in effectiveness and less in recurrence rate than intralesional vitamin D3.