Objectives: Numerous studies have been conducted on the clinical efficacy of immunotherapeutic agents in the treatment of cutaneous warts showing variable results. The present study aimed to compare the clinical efficacy and safety of intralesional tuberculin purified protein derivative (PPD) and Vitamin D3 therapy in recurrent and recalcitrant extra-genital cutaneous warts. Material and Methods: This study was conducted as a prospective, randomized, comparative, and single-blind study. A total of 104 patients were randomly distributed into two treatment groups: Group A (Tuberculin PPD, n = 53) and Group B (Vitamin D3, n = 51). Each patient in Group A received an intralesional injection of 0.1 mL tuberculin PPD (5 Tuberculin Units), while each patient in Group B received an intralesional injection of 0.2 mL Vitamin D3 (Cholecalciferol containing 120,000 IU). The injections were given at the initial visit (week 0) and after every 2 weeks for a maximum of four sessions (weeks 2, 4, and 6). The largest wart was selected for intralesional therapy. The categorization of clinical response was done based on the percent reduction in the size of warts into complete (appearance of normal skin), marked (>50% reduction), moderate (<50% reduction), and inadequate (no change in warts) responses. Adverse effects (if any) were recorded during each patient visit. The final response was evaluated at 6 months follow-up from the last treatment session. Results: Regarding the response of patients to tuberculin PPD therapy, out of a total of 53 patients, 40 (75.5%) showed a complete response. Regarding the response of patients to Vitamin D3 therapy, out of a total of 51 patients, 36 (70.6%) showed a complete response. However, the difference in the response to the treatment between the two groups was statistically insignificant (P = 0.402). Conclusion: Both intralesional tuberculin PPD and Vitamin D3 are effective and safe in the treatment of all recurrent and recalcitrant extra-genital cutaneous warts.