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Introduction: Warts are caused by the human papillomavirus (HPV), which infects the epidermal cell layers leading to their hyperproliferation. The concept of immunotherapy has recently come to light. It acts by mounting delayed cell-mediated and humoral immunity against the HPV in the host. Objective: This study aimed to evaluate the efficacy and safety of the intralesional PPD versus intralesional vitamin D3 for the management of recalcitrant warts. Materials and Methods: This prospective randomized trial was conducted on patients between the ages of 12 and 65 years with two or more recalcitrant extragenital warts. The subjects were randomly divided into two groups, namely, group A (PPD) and group B (vitamin D3). In group A, a purified protein derivative (PPD) of tuberculin was employed without any prior pre-sensitization testing. Each patient in group I received 0.1--0.2 mL of antigen at the base of the largest wart. In group B, the patients received 0.1--0.2 mL in a similar manner. Results: In group A, 39 (78%) patients had complete clearance while, in group B, 38 (76%) had complete clearance in injected warts (p = 0.8). As far as distant warts were concerned, in group A, 35 (70%) had a complete response while, in group B, 29 (48%) had a complete response. There was a statistically significant difference between the two groups with a greater degree of clearance in distant warts with the tuberculin PPD (p = 0.04). Conclusion: Both the tuberculin PPD and vitamin D3 are reliable and safe management options for recalcitrant, treatment-resistant, and extensive warts. [ABSTRACT FROM AUTHOR]