Background Intralesional immunotherapy has been reported to be effective for warts and to show good safety profiles, but this has not yet been systematically studied. Aims To determine the efficacy and safety of intralesional immunotherapy for treating non-genital warts. Methods We comprehensively searched the MEDLINE, Embase, Web of Science and Cochrane Library databases from the times of their inception to January 3, 2020. The primary outcome was the rate of complete response of all lesions. The distant complete response rate of warts located in an anatomically different body part and the recurrence rate were also analyzed. Results A total of 54 prospective studies was ultimately included. The immunotherapeutic agents used were Mycobacterium w vaccine, measles, mumps and rubella vaccine, purified protein derivative, Candida antigen, interferon, bacillus Calmette-Guérin vaccine and others. The pooled rate of complete response among all patients with non-genital warts treated using intralesional immunotherapy was 60.6% (95% confidence interval 54.8–66.5%). The pooled recurrence rate was 2.0% (95% confidence interval, 1.1–2.9%). All reported adverse events were mild and transient. Limitations The heterogeneity among studies Conclusion Intralesional immunotherapy is suggested for use in patients with multiple warts, given its promising results, good safety profile and low recurrence rate.