Background: Intralesional immunotherapy using different types of antigens is considered an effective and safe treatment option for different types of warts. However, there are few studies that illustrate the use of these antigens in the treatment of periungual warts as a distinct type of warts. Objective: To evaluate the efficacy and safety of three antigens: measles, mumps, rubella (MMR) vaccine, Candida antigen, and purified protein derivative (PPD) in the treatment of periungual warts. Methods: The study included 150 patients who were randomly assigned to 3 groups with 50 patients in each. Each agent was injected intralesionally at a dose of 0.1 mL into the largest wart at 2-week intervals until complete clearance or for a maximum of 5 sessions. Results: Complete clearance of warts was observed in 70%, 80%, and 74% in PPD, Candida antigen, and MMR vaccine groups, respectively. There was no statistically significant difference regarding the therapeutic response between the 3 studied groups. Adverse effects were transient and insignificant in the 3 groups. No recurrence of the lesions was reported in any of the studied groups. Conclusions: Intralesional antigen immunotherapy seems to be an effective therapeutic option for the treatment of periungual warts.