Background: Recalcitrant warts represent a frustrating challenge for both patients and physicians. Although many destructive and immunotherapeutic modalities are available for the treatment of warts, an ideal, universally effective approach has not been explored to date. Recently, intralesional antigen immunotherapy has shown promising efficacy in the treatment of warts. The aim of the study was to evaluate the efficacy and safety of intralesional measles, mumps, and rubella (MMR) vaccine in the treatment of recalcitrant warts. Methods: The study included 70 adult patients with multiple recalcitrant extragenital warts of different sizes and durations, with or without distant warts. They were directly injected, without a pre-sensitization skin test, with 0.3 intralesional MMR vaccine into the largest wart at 2-week intervals until complete clearance or for a maximum of five treatments. Follow-up was made every month for six months to detect any recurrence. Results: Sixty-five patients, 35 men and 30 women, completed the study, and five patients discontinued for various reasons. Complete clearance of the lesions was observed in 41 patients (63%), partial response in 15 patients (23%), and no response in nine patients (14%). Complete response was demonstrated in 74.5% of those presenting with distant warts. Side effects were mild and insignificant in the form of pain during injection, itching, erythema, and edema at the site of injection and flu-like symptoms. Recurrence was detected in two patients only. Conclusions: Intralesional immunotherapy by MMR vaccine is a promising, effective, and safe treatment modality for recalcitrant warts.