Treatment of recalcitrant plantar warts represent a highly challenging issue for both patients and physicians. Candida antigen and purified protein derivative (PPD) have shown promising efficacy in the treatment of warts, however no previous studies have compared both antigens for recalcitrant plantar warts. To assess the efficacy and safety of intralesional Candida antigen versus intralesional PPD in the management of recalcitrant plantar warts. The study included 120 adult patients with multiple recalcitrant plantar warts. They were randomly assigned to one of three groups; Candida antigen, PPD, or normal saline. Injections into the largest wart were repeated every 2 weeks until clearance or for a maximum of five sessions. Complete wart clearance was reported in 33 patients (82.5%) of the Candida antigen group, in 22 patients (55.6%) of the PPD group, and in one patient (5%) of the control saline group. A statistically significant difference was found between the studied groups in favor of Candida antigen. Adverse effects were mild and insignificant in the three groups. Intralesional antigen immunotherapy by Candida antigen or PPD is a promising, safe, and cost-effective therapeutic option for multiple recalcitrant plantar warts, with statistically significant superiority of Candida antigen.