Intralesional immunotherapy by different antigens has shown promising efficacy and safety in the treatment of warts. However, the use of these antigens for the treatment of plane warts has been investigated in two studies only. To evaluate the efficacy and safety of three antigens; Measles Mumps, Rubella vaccine (MMR), Candida antigen, and purified protein derivative (PPD) in the treatment of multiple plane warts. The study included 120 patients who were randomly assigned to three groups, 40 patients in each group. 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 five sessions. Complete clearance of warts was observed in 55% of the PPD group, in 70% of the Candida antigen group, and in 62.5% of the MMR group. No statistically significant difference in the therapeutic response was found between the three groups. Intralesional antigen immunotherapy seems to be a promising well-tolerated and effective therapeutic option for the treatment of multiple plane warts, with relatively higher efficacy of Candida antigen.