Background Genital warts caused by human papillomavirus (HPV) are one of the most common sexually transmitted infections. Long latency, lesions' multiplicity, high recurrence rate, and the tendency to malignant transformation are essential challenges during management. Traditional treatment modalities are known to be lesion‐directed while intralesional immunotherapy was introduced to act beyond individual lesions and to confront the previous challenges through injection of known antigens, such as measles, mumps and rubella (MMR) vaccine, to stimulate the immune system against HPV. Needling‐induced autoinoculation is also considred as an immunotherapeutic procedure that does not include the injection of antigens. We evaluated the efficacy of needling‐induced autoinoculation in the management of genital warts. Methods Fifty patients with multiple recurrent (≥4) genital warts were divided into two equal groups. One group was subjected to needling‐induced autoinoculation and the other was subjected to intralesional MMR injection every 2 weeks for a maximum of three sessions. Follow‐up was done for 8 weeks after the last session. Results Both needling and MMR showed statistically significant therapeutic outcome. Needling showed significant improvement with regard to the number (P = 0.000) and size (P = 0.003) of lesions. In parallel, MMR showed significant improvement with regard to the number (P = 0.001) and size (P = 0.021) of lesions. There was no statistically significant difference between both treatments outcomes in regard to number (P = 0.860) and size (P = 0.929) of lesions. Conclusions Both needling and MMR are effective immunotherapeutic modalities in management of genital warts. Needling‐induced autoinoculation, being more safe and inexpensive, may be considered as a competing choice.